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The effect of desoxycorticosterone on the height of normal thyroid epithelium
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The effect of desoxycorticosterone on the height of normal thyroid epithelium

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Content THE EFFECT OF DESOXYCORTICOSTERONE ON THE
HEIGHT OF N0RI'4AL THYROID EPITHELIUM
A T h e s is
P r e s e n t e d to
th e F a c u l t y o f th e D epartm ent o f Zoology
U n i v e r s i t y o f S o u th e rn C a l i f o r n i a
In P a r t i a l F u l f i l l m e n t
o f t h e R e q u ire m e n ts f o r th e D egree
M a ste r o f S cien ce
Kah-King Wong
Ju ne 1949
U M I Number: EP67177
All rights reserved
INFORMATION TO ALL USERS
The quality of this reproduction is dependent upon the quality of the copy submitted.
In the unlikely event that the author did not send a complete manuscript
and there are missing pages, these will be noted. Also, if material had to be removed,
a note will indicate the deletion.
UMI
D issyrtation P ublisN ng
UMI EP67177
Published by ProQuest LLC (2014). Copyright in the Dissertation held by the Author.
Microform Edition © ProQuest LLC.
All rights reserved. This work is protected against
unauthorized copying under Title 17, United States Code
ProQuest LLC.
789 East Eisenhower Parkway
P.O. Box 1346
Ann Arbor, Ml 48106- 1346
n/
This thesis, written by
EAH-KING L 'O N G
under the guidance of hA^... Faculty Committee,
and approved by all its members, has been
presented to and accepted by the Council on
Graduate Study and Research in partial fulfill­
ment of the requirements for the degree of
LIAST3R OF SCIZICCE
,.Smqr.y...S.»...3p^axlus.,
D EA N
Date................... J .U îlÿ ...l9 .A9 ..
Faculty Committee
Chairman
ACKNOWLEDGMENT
F or th e acco m p lish m en t o f t h i s t h e s i s I aia much
i n d e b t e d to Dr. F. M. B aldw in f o r h i s c h e e r f u l h e lp and
f r i e n d l y a d v ic e and encou ragem ent. I am a ls o g r a t e f u l to
Dr. T. W. R o b e rts and Dr. H. A. Tucker f o r t h e i r valua-ble
s u g g e s t i o n s and p e r s o n a l i n t e r e s t . I w is h a ls o t o th a n k
C ib a P h a r m a c e u tic a l P r o d u c ts , In c . and S o b e rin g C o rp o ra tio n
f o r t h e i r k in d c o o p e r a tio n i n s u p p ly in g me w ith a l l th e
d e s o x y c o r t i c o s t e r o n e a n e t s t e needed f o r t h e e x p e r i m e n t s .
TABLE OF CONTENTS
CHAPTER PAGE
I . INTRODUCTION .................................................................................. 1
The re v ie w o f l i t e r a t u r e .............................................. 1
Consum ption o f s u g a r s ...................................  2
A b s o r p tio n o f c a r b o h y d r a te s .................................... 3
S o u rc es o f g ly co g e n ........................................................ 5
The l i v e r .................................................................................. 6
C a rb o h y d ra te m e ta b o lism ................................................... 6
Role o f th e t h y r o i d g la n d and d e s o x y c o r t i c o s ­
t e r o n e ....................................................................................... 10
T h y ro id h o r m o n e s .............................................................. 10
D e s o x y c o r ti c o s t e r o n e ................................................... 11
E f f e c t on l i v e r g ly c o g e n a s e .................................... 11
E f f e c t on b lo o d s u g a r and g ly co g e n . . . . 12
Loss o f body w e i g h t ......................................................... 14
L iv e r g l y c o g e n ................................................................... 15
D e c re a se in l i f e s p a n ................................................... 16
M uscle g lycogen c o n te n t .............................................. 17
P h o s p h o r y la tio n o f glycog en by m u scles . . 18
I n f l u e n c e on h e a r t glycogen .................................... 21
I n c r e a s e in i n s u l i n ........................................................ 21
R e l a t i o n to p a n c r e a t i c d i a b e t e s .......................... 22
L i b e r a t i o n o f g ly c o g e n .............................................. 22
11
CHAPTER PAGE
A c t i v a t i o n of s u c c i n i c d e h y d ro g e n a se . . . 23
O x id a tio n m etab o lism ................................................... 24
The r e g e n e r a t i o n o f t i s s u e s .  .......................... 24
E f f e c t on b a s a l m e t a b o lic r a t e ......... 26
A d re n a l c o r te x v e r s u s t h y r o i d g la n d . . . . 2?
I I , EXPERIMENTATION............................................................ 28
The p r o p e r t i e s o f d e s o x y c o r t i c o s t e r o n e . . 28
I n j e c t i o n of d e s o x y c o r t i c o s t e r o n e ..................... 28
The e x p e rim e n ta l a n im a ls ......................................... 29
T hyroidectom y ........................................................................ 30
The m easurem ent o f th e t h y r o i d e p ith e liu m . 31
The m aking o f s l i d e s ...................................................
D e l a f i e l d ' s h e m a to x y lin - e o s in method . . . 33
S i l v e r method o f Da F a n o ......................... 35
B e n s l e y ’ s m e t h o d ...................................................  36
Regaud * s m e t h o d .................................................. 37
H e n sley * s b r a z i l i n - W a s s e r b l a u method . . . 38
I I I . RESULTS  .................................................................................. 40
The norm al c o n t r o l r a t s ............................................. 40
The r a t s r e c e i v i n g 10 mgs hormone p e r kg . 40
The r a t s r e c e i v i n g 20 mgs/kg o f hormone . . 41
The i n f l u e n c e o f age on th e h e i g h t o f
e p i t h e l i u m ....................................................... 42
The i n f l u e n c e of s e x ................................................ 42
I l l
CHAPTER PAGE
The i n f l u e n c e o f th e tim e e l e m e n t ..................... 43
S u m m a r y ....................................................................................... 44
G r a p h s ............................................................................................ 64
P l a t e s ............................................................................................. 67
BIBLIOGRAPHY....................................................................................................... 75
LIST OF TABLES
iv
PAGE TABLE
I . R e s u l ts O b ta in e d from Normal C o n tr o l R ats
w hich R e ceiv ed no I n j e c t i o n s o f Hormone . . . 48
I I . R e s u l ts O b ta in e d from Young Fem ale Normal
C o n tro l R a t s .................................................................................. 49
I I I . R e s u l t s O b ta in e d from Old Male Normal C o n tro l
Rat s ....................................................................................................... 50
IV. R e s u l ts from R a ts w hich R eceived 10 mgs/kg Body
W e i g h t ................................................................................................. 51
V. Old Female R ats w hich R eceived 10 mgs Hormone/
kg WT....................................................................................................... 52
V I. Old Male R a ts w hich R e ce iv e d 10 m gs/kg Wt. . . . 53
V I I . Young Fem ale R ats w hich R e ceiv ed 10 mgs/kg- Body
W e i g h t ................................................................................................. 54
V I I I . R a ts w h ich R eceiv ed 20 mgs Hormone p e r kg: o f
Body W e i g h t ........................................................   55
IX. Young Female R ats w hich R e ceiv ed 20 mgs/kg
Body W e i g h t .................................................................................. 56
X. Old Male R a ts w hich R e c e iv e d 20 mgs Hormone/kg
Body W e i g h t .................................................................................. 57
X I. R ats R e c e iv in g 10 mgs Hormone p e r kg Body W eight 58
X II . R ats R e c e iv in g 20 rags/kg H o r m o n e ...................................... 59
X I I I . R ats R e c e iv in g 10 m gs/kg H o r m o n e ..................................... 60
XIV. R ats R e c e iv in g 20 m gs/kg H o r m o n s ..........................  6 l
TABLE
XV. Rat 3 R e ce 1VIna 10 m_s /k a He rmone
V
PAGE
62
XVI. R ets Recelvln;-: 20 XiZs/A::' Hoiirone
CHAPTER I
I . INTRODUCTION
Much work has been done on th e a d r e n a l end th e
t h y r o i d g la n d s a s f a r as t h e i r b io c h e m i s t r y and t h e i r
p h y s io lo g y i s c o n c e rn e d , b u t th e e f f e c t o f d e s o x y c o r t i c o s t e r ­
one on th e h e i g h t o f th e t h y r o i d e p it h e l i u m has y e t to be
c l a r i f i e d . Both d e s o x y c o r t i c o s t e r o n e and th e t h y r o i d g la n d
have e f f e c t s on c a r b o h y d r a te , m in e r a l and t i s s u e m e ta b o lism .
T h is hormone may a c t d i r e c t l y on th e m etab o lism o r I n d i r e c t l y
th ro u g h th e t h y r o i d g la n d o r th e p i t u i t a r y g la n d . The o b j e c t
o f t h i s work i s to f i n d o u t i f t h i s p a r t l c u l a . r hormone o f th e
a d r e n a l g la n d has a. d e m o n s tra b le e f f e c t on th e h e i g h t o f th e
t h y r o i d e p it h e l i u m .
The re v ie w o f l i t e r a t u r e forms an e s s e n t i a l p a r t o f
t h i s work s in c e th ro u g h i t one becomes a c q u a in te d w i t h th e
work t h a t has been done in t h e p a s t on th e v a r i o u s e f f e c t s
o f d e s o x y c o r t i c o s t e r o n e and t h e t h y r o i d g la n d .
I I . THE REVIEW OF LITERATURE
The c o m p a ra tiv e a c t i v i t i e s o f th e a d r e n a l and th e
t h y r o i d g la n d s i s n e c e s s a r y h e r e f o r an u n d e r s t a n d i n g o f th e
p o s s i b l e I n t e r a c t i o n betw een th e d e s o x y c o r t i c o s t e r o n e end
th e t h y r o i d e p it h e l i u m . Among t h e s e a c t i v i t i e s a re th e
r o l e s th e y p la y in th e c a r b o h y d r a te m etab o lism ( in w hich may
be in c lu d e d th e consum ption o f s u g a r s , a b s o r p t i o n o f c a rb o ­
h y d r a t e s , s o u r c e s o f g ly co g e n and th e r e a c t i o n s w hich tsJce
p l a c e in th e body) and o t h e r m e ta b o lic r e a c t i o n s .
Consum ption o f s u g a r s . I t has b een assumed by many
t h a t th e blo o d s u g a r l e v e l i s r e s p o n s i b l e f o r th e s e n s a t i o n
o f h u n g e r and f o r su g a r con sum p tion . S o u l a i r a c , ^ how ever,
t h i n k s t h a t th e consum ption o f su g a rs depen d s on th e
i n t e s t i n a l a b s o r p t i o n o f them , and t h a t th e a b s o r p t i o n i s
g r e a t l y i n f l u e n c e d by v a r i o u s e n d o c rin e g la n d s . In h i s
e x p e rim e n ts w ith r a t s , he fou nd t h a t th e a d m i n i s t r a t i o n o f
i n s u l i n r e s u l t e d in a g r e a t in c r e a s e in th e i n t e s t i n a l
a b s o r p t i o n of suge.rs and t h e r e f o r e a much g r e a t e r v o l u n ta r y
co nsum ption . A f t e r th y ro id e c to m y t h e r e was a sh a rp d e c r e a s e
in t h e consum ption o f s u g a r s , b u t upon f e e d i n g t h y r o x in e
t h e r e was an i n c r e a s e . A drenalectom y and d e s o x y c o r t i c o s t e r ­
one a c e t a t e had th e same e f f e c t as th y ro id e c to m y and
t h y r o x i n e .
Richter,2^3 on th e o t h e r hand, in his work w i t h r a t s
found that a d re n a le c to m y c a u s e d them to d e c r e a s e t h e i r
^ Andre S o u l s i r a c , Compt. Rend. , 224:961-963» 1947.
^ C urt P. R i c h t e r , P r o c . S o c . E x p t l . B i o l . Med. ,
4 8 :5 7 7 - 9 , 1941.
3 C urt P. R i c h t e r , George H. Bunch, J r . , Howard E.
Wooden, J r . , E n d o c r in o lo g y , 2 9 :1 1 5 -2 5 , 1941.
3
i n t a k e o f g l u c o s e , b u t to i n c r e a s e t h e i r i n ta k e o f 7 > % s a l t
s o l u t i o n . D a ily t r e a tm e n t w i t h d e s o x y c o r t i c o s t e r o n e
d e c r e a s e d t h e i r w a te r and sodium c h l o r i d e in ta k e to norm al
and i n c r e a s e d t h e i r g lu c o s e i n t a k e to n e a r l y n o rm a l.
A b s o rp tio n o f c a r b o h y d r a t e s . The c a r b o h y d r a te s a re
a b s o r b e d in th e form o f h e x o se s th ro u g h th e v i l l i o f th e
s m a ll i n t e s t i n e . The h e x o se s t h a t a re a b so rb e d a re changed
i n t o g ly co g e n in th e l i v e r to a l a r g e e x t e n t and a l s o s t o r e d
t h e r e .
The r a t e a t w hich t h e d i f f e r e n t h e x o se s a re a b s o rb e d
v a r i e s w i t h d i f f e r e n t h e x o s e s . The g a l a c t o s e i s a b s o rb e d
a t t h e fs .8 te s t r a t e , th e n g l u c o s e , and th e n f r u c t o s e and
th e s lo w e s t o f a l l th e s e i s m annose. N orm ally g lu c o s e i s
a b s o r b e d more r a p i d l y th a n a p e n to s e , b u t in abnorm al
c o n d i t i o n s o f th e stom ach o r th e i n t e s t i n e s a p e n to s e i s
som etim es a b s o rb e d more q u i c k l y th a n g lu c o s e .
Both t h y r o x in e and d e s o x y c o r t i c o s t e r o n e have f a v o r a b l e
e f f e c t s on a b s o r p t i o n . G ra u e r, S ta r k e y and S a i e r ^ fou nd
t h a t d a i l y i n j e c t i o n s o f t h y r o x in e i n to dogs i n c r e a s e d th e
r a t e o f a b s o r p t i o n o f g a l a c t o s e from th e i n t e s t i n a l t r a c t
d u r i n g th e f i r s t seven d a y s . T his a b i l i t y was d e c r e a s e d
a f t e r f o u r t e e n d ay s b u t was r e g a in e d in tw e n ty d a y s .
^ R obert C. G rau er, Wm. F. S ta r k e y and E le a n o r Se 1 e r,
E n d o c r in o lo g y , 30 :4 7 4 -8 2 , 1942.
4
T h y ro x in e , h o w e v e r, g iv e n f o r s i x t e e n to tw en ty -tw o days
p ro d u c e d l i v e r damage w ith th e r e s u l t i n g i n c r e a s e in blood
g a l a c t o s e . Van N ienw enhuizen3 found t h a t d e s o x y c o r t i c o s t e r ­
one d e f i n i t e l y im proved th e a b s o r p t io n r a t e o f c a r b o h y d r a te s
and f a t s in an a c ro m e g a lic p a t i e n t .
When an e x p e r im e n ta l r a t i s h y p o p h y se cto m iz e d , th e
r a t e a t w hich i t a b s o rb s g lu c o s e i s d e c r e a s e d . R u s s e l l ^ in
h i s work on r a t s l e a r n e d t h a t th e i n t r e p e r i t o n e s l i n j e c t i o n
o f th y r o x in e i n t o h ypo phy secto m ized r a t s r e s t o r e d th e r a t e
o f a b s o r p t i o n o f g lu c o s e from th e i n t e s t i n e c o m p le te ly to
n o rm a l. He t h i n k s t h a t t h i s t r e a tm e n t d o e s n o t improve th e
m a in te n a n c e o f t h e c a r b o h y d r a te s t o r e s d u r i n g f a .s tin g o r
change th e p r o p o r t i o n a t e d i s p o s i t i o n o f th e a b so rb e d g lu c o s e
in t h e hyp oph y secto m ized r a t s . F o r n a r o l i and L e p o r a ti ^ of
th e U n i v e r s i t y o f P a v ia in I t a l y in t h e i r work w i t h th e
g u in e a p ig s found t h a t th e r a t e s o f a b s o r p t i o n o f g lu c o s e
and p e p to n e were a p p ro x im a te ly th e same f o r th e norm al and
th e t h y r o i d - t r e a t e d g u in e a p i g s , b u t th e y were somewhat
s lo w e r in th e t h y r o id e c t o m iz e d a n im a ls . I t was c o n clu d ed
3 L. C. van N ienw enhuizen, A cta Med. S c an d . , 108:
1 0 6 -1 6 , 1941.
^ Ja n e R u s s e l l , A m erican J . P h y s i o l . , 1 2 2 :5 4 7 -5 5 0 ,
1938.
3 P. F o r n a r o l i and I . Fab l e t t i L e p o r a t i , B o l l . s o c .
i t a l . b i o l . s p e r . , 1 5 :1 0 7 9 -1 0 6 1 , 1940.
5
a l s o t h a t th e r a t e o f a b s o r p t i o n o f x y lo s e was th e same f o r
th e normad, t h y r o i d - t r e a t e d and th y r o id e c to m iz e d g u in e a p ig s
S ources o f g ly c o g e n . I t i s known t h a t th e t h r e e main
f o o d s t u f f s — c a r b o h y d r a t e s , f a t s and p r o t e i n s — may c o n t r i b u t e
u n d e r f a v o r a b l e c o n d it i o n s t o th e f o r m a tio n o f g ly c o g e n in
th e body. The c a r b o h y d r a te s a r e b ro k en down to s im p le r
s u g a r s in th e m outh and th e n to h e x o ses l i k e g l u c o s e ,
g a l a c t o s e , f r u c t o s e , mannose end a ls o to p e n to s e s in th e
i n t e s t i n e . These a re a b s o r b e d i n to th e b lo o d stre a m
d i r e c t l y o r i n d i r e c t l y th r o u g h th e ly m p h a tic system and
c o n v e r te d to g ly c o g e n and s t o r e d in th e l i v e r o r in th e
m u s c le . Some o f th e s e s i m p l e s t su g a rs a r e o x i d iz e d i n t o
c a rb o n d io x id e and w a te r .
The f a t s a r e broken down to one m o le c u le o f g l y c e r o l
and t h r e e m o le c u le s o f f a t t y a c i d s in th e sm a ll i n t e s t i n e .
These com ponents o f f a t s a.re a b so rb e d a l s o in th e s m a ll
i n t e s t i n e . The g l y c e r o l m o le c u le s t h a t a r e a b so rb e d a r e
p a r t l y combined a g a in w ith t h e f a t t y a,cids to form b lo o d
l i p i d s and p a r t l y changed to g ly c o g e n .
The p r o t e i n s a r e d e g ra d e d i n to s im p le r form s in th e
sto m ach and f i n a l l y in to amino a c id s in th e sm a ll i n t e s t i n e
and a b so rb e d t h e r e . Among t h e amino a c i d s t h a t p l a y a p a r t
in t h e m etab o lism and in th e f o rm a tio n o f g lycog en a r e
g l u ta m ic a c i d , c y s t i n e , ad an i n e , s e r i n e , a s p s .r tic a c i d and
p r o l i n e .
6
B e sid e s th e t h r e e m ain f o o d s t u f f s a number o f t h r e e -
c a rb o n compounds in th e body ta k e a p a r t in th e f o r m a tio n of
g ly c o g e n and a ls o in th e c a r b o h y d r a te m e ta b o lism . They a re
d i h y d r o x y - e c e t o n e , l a c t i c a c i d , p y r u v ic a c i d , p y ru v ic
a ld e h y d e and o t h e r s . The s t r u c t u r a l fo rm u la s o f some o f
t h e s e comnounds a r e shown in F ig u re 2.
The l i v e r . Among th e many f u n c t i o n s o f th e l i v e r i s
th e s t o r a g e o f g ly co g e n (g ly c o g e n r e s e r v e ) . The c o n t r o l l i n g
f a c t o r in th e c o n c e n t r a t i o n o f g lu c o s e in th e b lo o d i s th e
c o n v e r s io n o f l i v e r g ly co g en (bu t not th e m uscle g ly co g en )
to g lu c o s e . In th e l i v e r i s found an enzyme w hich c a u s e s
th e breakdown o f glycogen to d e x t r i n and m a lto s e . This
enzyme i s known as l i v e r g l y c o g e n a s e .
I I I . CARBOHYDRATE METABOLISM
B efo re l e a r n i n g a b o u t th e r o l e and e f f e c t o f th e
t h y r o i d g la n d s and d e s o x y c o r t i c o s t e r o n e , i t i s b e n e f i c i a l to
p r e s e n t a, v e ry g e n e r a l c o n c e p t o f th e m etab o lism o f th e
c a r b o h y d r a t e s . The m etab o lism in v o lv e s a g r e - t many r e a c ­
t i o n s and a number o f enzymes to c a t a l y z e th e s e r e a c t i o n s .
The g ly c o g e n in th e b lo o d r e a c t s w ith p h o sp h a te to
form g lu c o 8e - l - p h o s p h a t e , th e r e a c t i o n b e in g c a t a l y z e d by
p h o s p h o r y la s e and a d e n y lic a c i d . The g l u c o s e - l - p h o s p h a t e i s
changed to z l u c o s e -6 -o h o s o h a te w ith th e h e lp o f
g l y c o g e n + p h osp h ate g/iicose-l-phosphote
I phosphoglwcom utase
glucose-è-phosphate -F—
glucose t- phosphate
g lu c o s e -t A T P
h e x o k ) y>ase
isonoerase
f r u c t o s e + A T P
fructose + phosphate
phosphate from acjenosme—
triphosphate (flXP9
r
fr u c to se - Lh Jip h osp h ate
rom nez'e on f r u t c
t e 1Ü d
- C ~ * : ^., .
v T k ' j L V .
co o H
(JHOH
l a c t i c a c id
4 + H
I ( j m u 5c k )
coori
c -o
CHs
pyruvic acid
COOH
I
COPO3 Hi­
ll
CHx
pho5ph(^pyruvic
acid
+ H % 0
IÎ
enolase
“ri:2 .0
Fr ucto5«.'I, h - cl I phosphate
î i
a -
COOH
CH0 PO3H ;
&H7.OH
plio^ploo-glycerit
Qcict
CH^tOPOaHz
9 0
CHaOH
I som e rase
1 - phos pho-di hsfàfox'j'
a c e t o n e
C o o H
I
C H O H
(iHxOPOjHa
~ H5PO 4
3 phosbho-gtyc&r'c
a c id
CHO
dHOH
CHxOPOjHx
3-phospho-olyco-
aldchyde
t i H3PO4
HCOHOPO3 H2.
énoH
cH i^ o PPbHi-
1,3-di phos pho-
glycero-aldcUyJc-
I
Coenz-Vrwe
C - r i . )
C0 0 PO3 H i
: CHOH
I
CHiOPPsHiL
1 ^ 3 -d i phos pho-
gly eerie aeicL
CHx— COOH
I ^
CHChiH^-coom
05Pft ftiC
CH3
C H 'N H x
(
COOH
olan i ne
1
C o-coo H
1
V
CHs
1 +
(i'O
GHz-COOH
GOOH
oxaloacetic
acid
pyruvic
acid
j
CHCOH)-COOH
I
CHx— COOH
m alic
aci(T
HxO
CH'tOOH
I I
C-tOOH <-
Î
C H - C O O H
II
CH-COOH
tu r a a r ic .
acid
CHx-COOH
I
CHx
I
CH(NHO'COOH
q l u t o
^ QCi(
m ic
C l
+1H
IÎ!
succinic
dehydroqenase
-ZH3
CHz'CO OH
CHt-COOH
5 u c c i n i c
ûcid
n
C O —COOH
CHz-'COOH
k e to -q lu ta r ic
Qcidr
ÇH5
CHOH
I
COOH
I a c -tic
acid
CHx -COOH
Crtz'CooH
C is - a e o n i t ic
a c i d
CH OH COOH
CH — COOH
CHx— C ooH
I SO - C i t r i C
a c id
- CHOH-COOH
I
CH%.— COOH
citric
Ac id
C O 'C O O H
-CO x, I
" " ------------- C H ' C O O H
CHz'COoH
o x alo -su ccin ic
a c i d
jTi'om uzT is r e a c t i o n s enown in inc&e t_:roo l'i,^ures one
:.n:'2^ liave a b e t t c i ' n n Je rita n o .ln ^ , of }.cw g l y c e r o l p o r t i o n of
f a t , c e r t a i n a n in o a.clon, anu eome t h r e e - c a r b o n cornponncLs
could, be oourcee o f ^.lycogen and c o u ld ta k e p a r t in th e
m e t a bo 11 an; of the c a.rb o hy dr a t e s .
IV. ROLE OF TRE TRYROIf GLAND r'.ND DELOXYCORTIGOBTLRONE
T hyroid h orm ones. At l e a a t t h r e e hormones have been
known to be p r e s e n t in th e t h y r o i d t i s s u e . They a re
d i i o d o t y r o s l n e , th y r o x in e and t b y r o g l o b u l I n . I t Is b e l i e v e d
t h a t two m o le c u le s o f d i l o d o t y r o s i n e r e a c t w ith each o t h e r
to form a m o le c u le o f t h y r o x in e w hich a g a in r e a c t w i t h th e
u n r e e c t e d d i l o d o t y r o s i n e and amino a c i d s to form a m o le c u le
o f t h y r o g l o o u l i n . The r e a c t i o n s among t h e s e compounds a re
i l l u s t r a t e d in th e f o llo w in g :
H o T V c H x - C H - C O O H + H o 7 ^ H t - C H - C O O H
2------------ Atk. 1 NH*.
diiodoèyrosine diiodLotyi^os'” ®
H o O - 0 - 0 < H . - C H - C o o H -thyroglobulin
I I (a. p r o t e i n )
"tK yroxine
11
D e s o x y c o r t i c o s t e r o n e . T his i s one o f th e many
horm ones o f th e a d r e n a l c o r t e x . I t i s a c t i v e m ainly in th e
s a l t m etab o lism a lth o u g h i t has some e f f e c t in th e c a rb o h y ­
d r a t e m etabolism a l s o . I t s s t r u c t u r a l form ula, i s shown as
f o l lo w s ;
C — CHzOH
C H t
CH3
0
E f f e c t on l i v e r g:lycoA‘e n a s e . L i v e r g ly c o g e n a s e i s an
enzyme w hich c a t a l y z e s th e breakdown o f l i v e r g ly co g e n to
d e x t r i n and m a l t o s e . The a d r e n a l c o r t e x hormone i n h i b i t s
th e a c t i v i t y o f t h i s enzyme w h ile th y r o x in e a c t i v a t e s i t .
The i n h i b i t i n g a c t i o n o f th e c o r t i c a l hormone on g ly c o g e n a s e
i s e l i m in a te d by th e t h y r o i d hormone a s w e l l as by a d re n a ­
l i n e s e c r e t e d by th e a d r e n a l m e d u lla . In a d d i t i o n to t h i s
a c t i o n th e t h y r o i d hormone a l s o a c t i v a t e s th e g ly c o g e n a s e ,
w h ich a.ctio n , t h e a d r e n a l i n e does n ot p o s s e s s . The e f f e c t
o f th e t h y r o i d hormone end a d r e n a l i n e i s s p e c i f i c a l l y on th e
l i v e r g ly c o g e n a s e b u t n o t th e am ylase o f p a n c r e a s . The
l i v e r g ly c o g e n a s e a c t s by p h o s p h o r o l y s i s w h ile th e p a n c r e a t i c
12
am ylase a c t s by h y d r o l y s i s . K o tly a ro v ^ in h i s i n v e s t i g a t i o n
fou nd t h a t th y r o x in e i n tr o d u c e d in v iv o as w e ll as by
a d d i t i o n in v i t r o , a c t i v a t e d l i v e r g ly c o g e n a s e l i b e r a t e d
from th e t i s s u e in a.queous m edia. The same a c t i o n was
o b s e rv e d in th e t h y r o i d g la n d by k e e p in g th e norm al a n im a ls
u n d e r c o n t r o l l e d c o n d i t i o n s , t h a t i s , on a mixed d i e t a t a
t e m p e r a tu r e o f 15^ C. His e a r l i e r work a.lso showed t h a t
s u p r a r e n a l hormones d e p r e s s e d th e l i v e r g ly c o g e n a s e s x t i v i t y
as shown by th e c u rv e o f t h e r a t e o f g l y c o g e n o l y s i s .
A d r e n a lin e and t h y r o x in e a c c e l e r a t e d th e a c t i v i t y and co u ld
be made to e l i m i n a t e c o m p le te ly th e m a n i f e s t a t i o n s o f th e
s u p r a r e n a l horm ones. A d r e n a lin e was c a p a b le o n ly o f
r e s t o r i n g th e a c t i v i t y o f g ly c o g e n a s e to th e norm al l e v e l
w h i l e th y r o x in e c o u ld r a i s e th e l e v e l above th e n o rm a l.
T h e r e fo r e he c o n c lu d e d t h a t t h y r o x in e was th e t r u e a c t i v a t o r
o f t h e l i v e r g ly c o g e n a s e .
E f f e c t on b lo o d s u g a r and g ly c o g e n . Both th e t h y r o i d
s e c r e t i o n and t h e d e s o x y c o r t i c o s t e r o n e i n c r e a s e th e b lo o d
s u g a r though d e s o x y c o r t i c o s t e r o n e e l e v a t e s i t o n ly s l i g h t l y .
The t h y r o i d s e c r e t i o n d e f i n i t e l y i n c r e a s e s th e b lo o d
g ly c o g e n .
In h i s e x p e rim e n ts w i t h th e norm al a d u l t male r a b b i t s
® I . I . K o tly a ro v ( L e s g a f t I n s t . , L e n in g r a d ) , J .
P h y s i o l . , ( U .S .S . R .), 3 2 :1 9 5 -4 0 3 , 1946. B y u l l . E k s p t l .
B i o l . M ed ., lL :N o .9 , 7 9 -8 2 , 1942.
13
Okat a n i 9 found t h a t th e f a s t i n g b lo o d g ly c o g e n was 3*5
m g s^. A f t e r f e e d i n g t h y r o i d f o r s e v e r a l days th e b lo o d
g ly c o g e n i n c r e a s e d d i s t i n c t l y , and th e b lo o d s u g a r te n d e d
to i n c r e a s e . A f t e r d i s c o n t i n u i n g t h y r o i d f e e d in g th e b lo o d
suga.r f e l l r a p i d l y , b u t th e b lo o d g ly c o g e n rem ained h ig h f o r
some tim e . B oth th e b lo o d s u g a r and th e b lo o d g ly c o g e n
te n d e d to d e c r e a s e a f t e r th y ro id e c to m y . In u n f a s t e d
c o n d i t i o n a w e l l known f u n c t i o n o f th y r o x in e i s to i n c r e a s e
th e b lo o d s u g a r l e v e l .
J a n e s and N elson^^ in t h e i r work w i t h f a s t e d a d r e n a l -
e c to m iz e d r a t s fo und t h a t t h e i r c a r b o h y d r a te l e v e l s w ere lo w ,
Even though t h e s e r a t s w ere m a in ta in e d on d e s o x y c o r t i c o s t e r ­
one a c e t a t e , th e b lo o d s u g a r v a lu e s w ere im proved o n ly
s l i g h t l y , and th e l i v e r g ly c o g e n l e v e l s w ere unchanged.
G-obell,^^ i n j e c t i n g i n t r a v e n o u s l y 10-20 mg.
d e s o x y c o r t i c o s t e r o n e in aqueous s o l u t i o n i n t o c h i l d r e n o f
s c h o o l ag e, found no e f f e c t on th e b lo o d s u g a r , b u t l a c t i c
and p y ru v ic a c i d s w ere lo w e re d . This lo w e r in g was e f f e c t e d
i n d i r e c t l y th r o u g h V itam in B ^ .
9 M. O k a ta n i, F o l i a E n d o c r i n o l . J a p o n . 1 4 :1 3 , 1938
( i n G erm an).
R alph G. J a n e s and W arren 0, N e lso n , J .
P h y s i o l . , 1 3 7 : 5 5 7- 6 3 , 1 9 4 2 .
I . 0. G o b e ll, K l i n . wochsc h r. 20: 825-7, 1947.
14
H a r ris o n and K s r r i s o n l 2 in t h e i r e x p e rim e n ts w i t h
a d r e n a le c to m iz e d r a t s found t h a t in th e u n t r e a t e d r a t s th e
b lo o d s u g a r l e v e l d ro pped. I n j e c t i o n s o f a d eq u a te amounts
o f d e s o x y c o r t i c o s t e r o n e a c e t a t e i n to f a s t e d a d re n a le c to m iz e d
r a t s p r e v e n te d a dro p in th e blood s u g a r c o n c e n t r â t i o n .
denes^3 in h i s e x p e rim e n ts w ith dogs found t h a t th e
h i g h e r th e b lo o d su g a r l e v e l th e s m a lle r i s th e amount o f
s u g a r e n t e r i n g th e blo o d from th e l i v e r . A dren alectom y o r
l i g a t i o n o f th e b lo o d v e s s e l s l e a d i n g to th e a d r e n a l g la n d s
d e c r e a s e d th e flo w o f su g a r from th e l i v e r . T his me.y
a c c o u n t f o r th e f a c t t h a t i n s u f f i c i e n c y o f th e a d r e n a l
g la n d s c au se s h yp oglycem ia.
Loss o f body w e i g h t . A nother e f f e c t o f t h y r o i d
s e c r e t i o n i s th e d e c r e a s e in body w e ig h t. H idekazu K ato^^
w o rk in g w ith r a b o i t s found t h a t f e e d in g w ith 0 .1 gram o f a
t h y r o i d p r e p a r a t i o n c a l l e d t h y r o i d i n t o g e t h e r w ith t o f u k a r a
d a i l y f o r t e n to tw en ty days d e c r e a s e d t h e body w e ig h t o f
h i s r a b b i t s , b u t a f t e r t o ts .l th y ro id e c to m y th e r a b o i t s
i n c r e a s e d in w e ig h t a f t e r e i g h t to t h i r t y - f i v e d a y s. He
fo u n d a ls o t h a t th e b lo o d o f t h y r o i d i n - f e d r a b b i t s had
12 H a ro ld £. H a r r is o n and H elen Co p lan H ai-riso n, P r o c .
S o c . E x p t l . B i o l . M ed., 4 2 :5 0 6 -8 , 1939.
13 s . G. Genes, J . P h y s i o l . , U . S . S . R . , 3 0 :5 3 4 -3 5 , 1941
1^ H idekazu K a to , M i t t . Med. A kad. K io to , 25: 715 -1 6,
1 9 39.
15
a lm o st th e norm al l e v e l o f s u g a r , b u t t h e b lo o d s u g a r o f th e
th y r o id e c to m iz e d ones was d e c r e a s e d s l i g h t l y . G lycogen in
th e m uscle o f th e t h y r o i d i n - f e d a n im als was d e c r e a s e d .
A f t e r th y ro id e c to m y th e g ly c o g e n of m u sc le s rem ains alm o st
un ch an ged.
L iv e r g ly c o g e n . T h y ro x in e i n f l u e n c e s th e m o b i l i z a t i o n
o f l i v e r g ly c o g e n w h ile d e s o x y c o r t i c o s t e r o n e has l i t t l e o r no
i n f l u e n c e . In t h e i r e x p erim e n t w ith r a t s A b e lin and A lth a u s l5
fo u n d t h a t g i v i n g an ex cess o f th y r o x in e to th e r a t s caused
a c o n tin u e d g ly c o g e n d e f i c i e n c y in th e l i v e r not s o l e l y due
to th e enhanced s u g a r consum ption s in c e t h e r e was n o t an
i n c r e a s e in e n e rg y p r o d u c t i o n . R ats r e c e i v i n g b o th th e
t h y r o i d and th e a d r e n a l hormone e x t r a c t s t o g e t h e r l a i d up an
a lm o st norm al amount o f l i v e r g ly cog en d e s p i t e pronoun ced
t h y r o i d t o x i c i t y . A d m i n is tr a t io n o f a d r e n a l e x t r a c t s to th e
h y p e r t h y r o i d a n im a ls d id n o t c o u n te r a c t th e lo w e rin g o f
g ly c o g e n by t h y r o x i n e .
A n o th er i n v e s t i g a t o r , K i u r a found t h a t i n j e c t i o n
of th y r o x in e i n c r e a s e d su g a r and l a c t i c a c i d in th e l i v e r
a r t e r i a l b lo o d , p o r t a l v e in b lo o d and h e p a r i c v e in b lo o d .
T h is shovfs t h a t t h y r o x in e c a u se d th e g ly c o g e n in th e l i v e r
^5 I , A b e lin and U. A lth a u s , H e l v . Chim. A c t a , 25:
2 0 5 -1 5 , 1942.
46 M inoru Miura., Tohoku J . L x p t l . Med. , 3 9 :2 7 8 -8 8 ,
1940.
16
to be m o b iliz e d end to be s e n t in to th e b lo o d th r o u g h th e
h e p a t i c v e in in th e form o f s u g a r end l a c t i c a c i d .
De Groot and O v e r b e c k ^ ^ t h e i r work w ith r a t s found
t h a t d e s o x y c o r t i c o s t e r o n e h as no i n f l u e n c e on th e g ly co g e n
c o n te n t o f th e l i v e r in th e norm al end t h e a d re n a le c to m iz e d
r a t s . C o r k i l l and Nelson^G fn t h e i r work w ith young r a b b i t s
a l s o found t h a t d e s o x y c o r t i c o s t e r o n e was i n a c t i v e in c a u sin g
a d e p o s i t i o n o f l i v e r g ly c o g e n . G r a tta n and J e n s e n 4 9 a ls o
fo u n d t h a t t h i s hormone had l i t t l e o r no i n f l u e n c e on th e
f o r m a tio n o f l i v e r g ly c o g e n . Corey and B r i tt o n ^ ^ in t h e i r
work w i t h i s o l a t e d r a t l i v e r s a ls o found t h a t i t d i d not
s t i m u l a t e g l y c o g e n e s is .
D e crease Iji l i f e s p a n . I t has b e en r e p o r t e d t h a t
t h y r o x in e c au se d a s h o r t e r l i f e span. Thaddea and
p i
Scharsa.ch in t h e i r e x p e rim e n t w ith g u in e a p ig s foun d t h a t
a d m i n i s t r a t i o n o f one m il l ig r a m o f th y r o x in e p e r k ilo g r a m of
47 A, P. de Groot and G. A. O verbeck, N e d e rla n d
T i.l d s c h r . Geneeskunde 90, I I , 671-3» 1946.
48 A. B. C o r k i l l and J . F. N e lso n , A u s t r a l i a n J .
E x p t l . B i o l . Med. S c i . , 1 9 :2 4 1 - 2 , 1941.
49 J. F. G r a tta n and J . J e n s e n , J . B i o l . Chem. , 135:
5 1 1- 1 7 , 1 9 4 0 .
20 E. L. Corey and S. W. B r i t t o n , t o . J . P h y s i o l . , I 3I
7 8 3 -9 , 1 9 4 1.
^4 s , Thaddea and F. S c liersach , Biochem . Z. , 3 0 5 :1 0 9 -
28, 1940.
17
body w e ig h t r e s u l t e d in a s h o r t e r l i f e span o f th e a n im a ls
on a norm al o r s c o r b u t i c d i e t th a n t h o s e w ith a norm al
t h y r o i d f u n c t i o n and s i m i l a r l y f e d . The l i f e span was no t
s h o r t e n e d i f a s c o r b i c a c i d was g iv en a t th e same tim e .
A f t e r th y ro id e c to m y th e a n im a ls s u r v iv e d l o n g e r th a n th o s e
h a v in g norm al t h y r o i d g la n d s when th e y w ere on e i t h e r th e
o r d i n a r y o r th e s c o r b u t i c d i e t . G iving th y r o x in e to th e s e
th y r o id e c t o m iz e d an im als a g a in s h o r te n e d t h e i r l i f e span .
M uscle g ly c o g e n c o n t e n t . W in ter and Thomson^Z
w o rk in g w ith th e g a s tro c n e m iu s m uscle o f th e i n t a c t o r
c a s t r a t e d male r a t found t h a t d e s o x y c o r t i c o s t e r o n e d id no t
a f f e c t th e c o n c e n t r a t i o n o f g ly co g en in t h i s m u sc le . In
a d r e n a l i n s u f f i c i e n c y d e s o x y c o r t i c o s t e r o n e d i d n o t r e s t o r e
th e low m uscle g ly co g en l e v e l s to n o rm al. On th e c o n t r a r y
M o n tig e l and V erza r^ 3 found t h a t a d r e n a le c to m iz e d c a t s
t r e a t e d w ith d e s o x y c o r t i c o s t e r o n e o f t e n a cc u m u lated more
g ly c o g e n in m u sc le s th a n d i d th e i n t a c t u n t r e a t e d c a t s .
Ja.nes and N elson^^ in t h e i r work w i t h f a s t e d a d r e n a l -
e c to m iz e d r a t s fou nd t h a t in such a n im a ls t r e a t e d w i t h
C h a rle s A. W in te r and J . D. Thomson, Proc S o c .
E x p t l . B i o l . M e d ., 5 5 :9 5 -7 , 19^4.
0. M o n tig e l and F. V e rz a r, H e l v . P h y s i o l .
P h a rm a c o l. A c t a , 1 :5 7 -4 1 , 1941.
R alph G. J a n e s and Warren 0. N e lso n , A, J . P h y s io l
1 5 7 :5 5 7 -6 3 , 1942.
18
d e s o x y c o r t I c o s t e r o n e a c e t a t e th e m uscle g ly co g e n v a l u e s v/ere
norm al o r s l i g h t l y e l e v a t e d . The l i v e r g ly co g en l e v e l s were
a l s o unchanged,
P h o s p h o r y la tio n o f g ly c o g e n by m u s c l e s . D e s o x y c o r ti-
C G sterone i s an im p o rta n t component o f t h e enzjmie sy stem which
p h o s p h o r y l a te s m uscle g ly c o g e n as shown by e x p e rim e n ts o f
M ontigel.-'-^ I t a c c e l e r a t e s th e p h o s p h o r y la tio n o f g ly co g en
by m u sc le s o f a d r e n a le c to m iz e d r a t s and r e s t o r e s i t to
n o rm a l, but i t d oes not a c c e l e r a t e th e p h o s p h o r y l a ti o n o f
g ly c o g e n by m u sc le s o f norm al r a t s . T his has been shown by
th e work o f V e rz a r and M o n t i g e l .
In h i s work w ith th e m uscle o f t h e norm al r a t s
D o e tsch ^ ^ found t h a t th e amount o f p h o s p h o r y l a ti o n o f
g ly c o g e n a t room te m p e r a tu re c o rre sp o n d e d to 41.6/^ o f f r e e
p h o sp h o ru s a f t e r f i f t e e n m in u te s and 5 9 . 4/u a f t e r t h i r t y
m in u te s . These f i g u r e s w ere th e a v e ra g e v a lu e s o f t h i r t y -
two e x p e rim e n ts . A nalogous date, f o r a d r e n a le c to m iz e d
a n im a ls was 28.4>1 and 8 4 . 1/i w h ich w ere th e a v e ra g e v a l u e s of
f i f t y - e i g h t e x p e r i m e n t s . T h e r e fo r e th e r a t e o f g ly c o g e n
25 c . Montigel, Helv. Chim. Acta, 26:883-905, 1943*
? «
I . F. Verzar and C. Montigel, Helv. Chim. Acta,
2 5 :9 - 2 1 ; H e lv . Chim. Acte, 2 5 :2 2 -2 9 , 1942.
R. Doetsch, Helv. Chim. A c t a , 2 8 :3 1 -4 1 , 1945*
19
p h o s p h o r y l a ti o n was d im in is h e d in a d r e n a le c to m iz e d a n im a ls .
Normal hungry a n im a ls showed no d e c r e a s e . C o n tro l e x p e r i ­
m ents p erfo rm ed on a n im a ls c h i l l e d to 4°C a ls o showed no
l e s s e n i n g o f th e r a t e o f p h o s p h o r y l a t i o n . S i m i l a r l y , th e
l i v e r o f a d re n a le c to m iz e d a n im a l p h o s p h o r y l a te d l e s s
g ly c o g e n th an t h e noimiel.
Muscle g ly c o g e n fo rm a t i o n . D e s o x y c o r ti c o s t e r o n e
a c c e l e r a t e s th e d e g r a d a t i o n o f m uscle g ly c o g e n , w h ile
t h y r o x i n e , a c c o rd in g to d i f f e r e n t w o r k e r s , has d i f f e r e n t
e f f e c t s on m u scle g ly c o g e n . S p e k to r^ ^ who worked w i t h 20o
young r a t s found t h a t a .fte r g iv in g 0 . 25/ o s o f th y r o x in e
t w ic e on th e same day and p e rfo rm in g t h e e x p e rim e n ts one day
a f t e r th e th y r o x in e t r e a t m e n t , th e s e a n im a ls r e t a i n e d th e
a b i l i t y to s t o r e g lyco gen i n th e l i v e r as w e ll a s t h e m uscle
The l i v e r g ly c o g e n in them a f t e r tw e n ty h o u rs o f s t a r v a t i o n
o r a f t e r s u g a r f e e d i n g was d e f i n i t e l y low^er th a n in th e
n o r m a l. The m u sc le g ly co g e n was h ig h e r th a n in th e no rm al.
L ie b ig ’^^ in h i s vjork w ith r a b b i t s found t h a t th y r o x in e
c a u se d a marked d e c r e a s e in h e a r t m uscle g ly co g e n and b,
g r e a t e r d e c o m p o s itio n o f th e s k e l e t a l m u sc le g ly c o g e n .
Ya. Z. S p e k to r, Med, e x p t l . ( U k r a in e ) , 8 : No. 2,
2 8 -3 5 , 1941.
Hans L ie b ig , Z. ^ e s . e x p t l . m ed. , 1 0 9 :7 1 5 -7 2 9 ,
1941. Ghem. Z e n t r . , I , 24 12-2413, 1943.
20
The work o f V e rz a r end W enner-^ * w ith th e diaphragm
m u sc le o f th e norm al and th e a d r e n a le c to m iz e d r a t s showed
t h a t d e s o x y c o r t i c o s t e r o n e a c c e l e r a t e d t h e break-dow n of
g ly c o g e n by i n c r e a s i n g p h o s p h o r y l y s i s . These w o rk e rs found
t h a t in th e l i v e a d r e n a le c to m iz e d r a t s d e s o x y c o r t i c o s t e r o n e
s t i m u l a t e d g ly co g e n f o r m a t i o n . In a n o th e r e x p e rim e n t o f
t h e i r s w ith th e r a t diaphragm th e y fou nd t h a t th e a d d i t i o n
o f 5 -1 0 mg’ d e s o x y c o r t i c o s t e r o n e p e r 100 cc o f R in g e r s o l u t i o n
in w hich th e diaphragm was immersed c a u se d th e g ly c o g e n o f
th e diaphragm to b re a k down. Even 1 mg/ of d e s o x y c o r t i c o s t e r ­
one c o m p le te ly i n h i b i t e d th e s y n t h e s i s o f g ly co g en from
g lu c o s e in R in g e r s o l u t i o n .
Mentha and V o e g tli^ ^ in t h e i r e x p e rim e n ts w i t h th e
m u sc le a t r e s t in th e g lu c o s e R in g e r s o l u t i o n form ed sm a ll
am ounts o f g ly c o g e n . When 5 mg/ o f d e s o x y c o r t i c o s t e r o n e was
added to th e b a t h f l u i d , th e r a t e o f g ly co g e n fo r m a tio n was
r e d u c e d to o n e - t h i r d . The a d d i t i o n o f 10 mg/ o f d e s o x y c o r-
t i c o s t e r o n e to th e b a th f l u i d s to p p e d g ly co g e n f o r m a tio n
c o m p le te ly .
F. Verzar and V. Wenner, Bull. soc. chim. biol.
2 9 :3 0 4 - 6 , 1947.
F. Verzar and V. W enner, Biochem. J . , 42:35-41,
1948.
32 J , Mentha and W. Voegtli, Helv. Physiol. et
Pharmacol. Acta 5» 0 4 3 -5 , 1947.
21
On th e o t h e r hand, R i e s s e r 3 3 in h i s e x p e rim e n ts w ith
i s o l a t e d r a t diaphragm found t h a t b o th d e s o x y c o r t I c o s t e r o n e
and an e x t r a c t o f th e a d r e n a l c o r t e x p ro v e d to have no
e f f e c t on th e g ly c o g e n c o n te n t o f th e d iap h rag m . He a ls o
fo u n d t h a t t h y r o x in e c a u se d a s l i g h t i n c r e a s e in g ly c o g e n
s y n t h e s i s even a f t e r th e s y n t h e s i s had been i n t e n s i f i e d by
i n s u l i n .
I n f l u e n c e on h e a r t g ly c o g e n . The e f f e c t o f t h y r o x in e
on th e h e a r t m u scle g ly co g e n i s d i f f e r e n t from th e e f f e c t on
t h e s k e l e t a l m u sc le g ly c o g e n . T his may be due to th e
d i f f e r e n c e in s t r u c t u r e s and c o m p o s itio n o f th e s e two ty p e s
of m u sc le , th e s k e l e t a l m u sc le b e in g v o l u n t a r y and s t r i a t e d
w h ile th e c a r d i a c m uscle i s i n v o l u n t a r y b u t s t r i a t e d .
O J I
L ie b ig - in h i s e x p e r im e n ta tio n on r a b b i t s found t h a t
t r e a t m e n t w ith th y r o x in e c a u s e d a m arked d e c r e a s e in th e
h e a r t g lycog en and a g r e a t e r d e c o m p o s itio n o f th e s k e l e t a l
m u sc le g ly c o g e n . The c a r b o h y d r a te o f th e myocardium o f th e
h e a r t was more r e s i s t a n t to th e a c t i o n o f t h y r o x in e th a n
t h a t o f th e s k e l e t a l m u s c le .
I n c r e a s e in i n s u l i n . S ince i n s u l i n i s o u t s t a n d i n g l y
1 9 4 7 .
33 o t t o R i e s s e r , B io ch im . e t B io p h y s . A cta, 1:208-33»
34 Hans L ieb im , 2. g e s . e x p t l . m ed. , 109:715-29» 1941
Ghem. Z e n t r . , 1943» I» 2 412 -1 3.
22
in v o lv e d w ith th e m etab o lism o f th e c a r b o h y d r a te s a l s o ,
t h e r e must be some k in d o f r e l a t i o n s h i p betw een i t and
t h y r o x i n e . H a is t^ ^ found t h a t a d m i n i s t r â t io n of th y r o x in e
to t h e e x p e r im e n ta l an im als caused an i n c r e a s e in th e pan­
c r e a t i c i n s u l i n . As i n s u l i n i s s e c r e t e d by th e B - c e l l s of
th e i s l e t s of L an g erh an s o f th e p a n c r e a s , t h i s i n c r e a s e in
s e c r e t i o n i s i n t e r p r e t e d a.s b e in g a s s o c i a t e d w i t h an
i n c r e a s e in th e volume o f t h e f u n c t i o n i n g B - c e l l s .
R e la ti o n to p a n c r e a t i c d i e .b e te s . The f u n c t i o n o f
i n s u l i n i s to e n a b le th e s u g a r in th e b lo o d to be b u rn e d and
to c a u se g ly co g e n formed from th e blood s u g a r to be
d e p o s i t e d in th e l i v e r . On t h e o t h e r h a n d , th y r o x in e
c a u s e s th e l i v e r gly co g en to be changed to th e b lo o d su g a r.
When th e p a n c r e a s a t r o p h i e s o r i s c o m p le te ly ta k e n o u t of
th e a n im als u se d f o r th e e x p e rim e n t, th e b a la n c e b etw een th e
two hormones i s u p s e t . T h e r e f o r e , d u r i n g p a n c r e a t i c
d i a b e t e s i n j e c t i o n o f t h y r o x i n e in to th e an im als a g g r a v a t e s
th e c o n d it i o n by r a i s i n g th e b lo o d s u g a r to an a b n o rm a lly
h ig h l e v e l .
L i b é r â t io n of p ly co m en . T h yroid hormone c a u s e s th e
l i b e r a t i o n o f g ly co g e n f o r t h e p u rp o se o f an i n c r e a s e d
35 R. E. H e i s t , P h y s i o l . Rev. . 2 4 :4 0 9 -4 4 , 1944
23
e n e rg y su p p ly , Somskov end Bausch^o w o rk in g w ith g u in e a
p i g s u se d thymus end t h y r o i d horm ones. He found t h a t th e
i n j e c t i o n o f thymus hormone c au se d no i n c r e a s e in th e
m e ta b o lism o f t h e s e a n i m a l s . T h y ro id and thymus hormones
t o g e t h e r b ro u g h t ab out th e m o b i l i z a t i o n o f l i v e r g ly c o g e n .
The l i b e r a t i o n o f th e g ly co g e n th ro u g h t h e i n f lu e n c e o f th e
t h y r o i d hormone ta k e s p la c e f o r th e p u rp o s e of an i n c r e a s e d
e n e rg y su p p ly , w h ile th e m o b i l i z a t i o n o f th e g ly co g en
t h r o u g h th e thymus hormone i s e f f e c t e d f o r th e p u rp o se o f
i n c r e a s e d d e p o s i t f o r g ro w th . T h e re fo re t h y r o id g i v e s r i s e
t o th e o x i d a t i o n m etab o lism and th^mius t h e b u i l d i n g - u p
m e ta b o lis m .
A c tiv â t io n o f s u c c i n i c d e h y d ro g e n a s e . As h as been
se en in F ig u r e 3» s u c c i n i c a c i d i s d e p r i v e d o f two hydrogen
atom s by th e c a t a l y t i c a c t i o n o f th e s u c c i n i c d eh y d ro g e n ase
and i s th e r e b y changed to f u m a ric a c i d . A l o i s i and
C a v e .l l i n i 3 7 in t h e i r i n v e s t i g a t i o n fo und t h a t o ld , p a r t l y
i n a c t i v a t e d p r e p a r a t i o n s o f s u c c i n i c d e h y d ro g e n ase system
from th e b e e f h e a r t were som etim es r e a c t i v a t e d , b u t th e
f r e s h p r e p a r a t i o n s o f t h i s enzyme was n o t a f f e c t e d by th e
36 C h r i s t i a n Bomskov and W illy B au sch, Z. h i i n . Med.
1 3 9 : 121- 6 , 1941; Ghem. Z e n t r . 1941, I , 3528.
37 A l o i s i , M. and D. C a v a i l i n i , U niv. Rome, B o l l . soc
i t a l . b i o l . s p e r . , 15: 661-682 , 1940.
24
a d d i t i o n o f th e t h y r o i d e x t r a c t . I t i s q u i t e p o s s i b l e and
a l s o p r o b a b le t h a t th e t h y r o i d hormone in th e b lo o d k eep s
th e s u c c i n i c d e h y d ro g e n a se a c t i v e .
O x id a tio n m e ta b o lis m . I t has a l r e a d y been m en tio n ed
t h a t th e t h y r o i d hormone e f f e c t s th e l i b e r a t i o n o f l i v e r
g ly c o g e n f o r o x i d a t i o n to g iv e an i n c r e a s e d su p p ly o f energy.
Bomskov end 3 a u s c h 3 8 i n j e c t e d th e t h y r o i d hormone and th e
thymus hormone i n t o th e g u in e a p ig s and found t h a t th e
i n j e c t i o n r e s u l t e d in th e m o b i l i z a t i o n o f l i v e r g ly c o g e n .
They found t h a t th e l i b e r a t i o n o f th e g ly c o g e n th ro u g h th e
i n f l u e n c e o f th e t h y r o i d hormone o c c u r r e d f o r th e p u rp o se o f
an i n c r e a s e d e n e rg y su p p ly . T h e re fo re t h e t h y r o i d hormone
f a c i l i t a t e s th e o x i d a t i o n m etab o lism .
A ccording to E v a n s 3 9 th e a d re n a le c to m iz e d r a t as
compared w ith c o n t r o l s l o s e s more c a r b o h y d r a te in t h e e a r l y
h o u rs o f f a s t i n g , s t o r e s l e s s g ly co gen when i n j e c t e d w ith
g lu c o s e o r g lu c o s e and i n s u l i n and has a norm al in tr a v e n o u s
g lu c o s e t o l e r a n c e . T his i s due to th e f a c t t h a t a d r e n a l e c ­
tomy i n c r e a s e s t h e te n d e n c y to o x id iz e c a r b o h y d r a t e .
The r e a e n e r a t i o n o f t i s s u e s . Des o x y c o e r t i c o s t e r o n e
C h r i s t i a n Bomskov and W illy B ausch, Z. K l i n . Med.
1 3 9 : 121- 6 , 1941.
3^ G e ra ld E vans, E n d o c rin o lo g y , 2 9 :7 3 1 -3 6 , 1941.
25
and th e t h y r o i d have somewhat d i f f e r e n t e f f e c t s on th e
r e g e n e r a t i o n o f t i s s u e s . The t h y r o i d g la n d prom otes
r é g é n é r â t io n j w h ile d e s o x y c o r t I c o s t e r o n e d i s t u r b s g ro w th by
c a u s i n g i r r e g u l a r d l s t r i o u t i o n o f th e chromosomes.
S p le s s -3 e r ts c h in g e r-4 0 p o iso n e d t h e norm al, t h y r o i d e c ­
to m iz e d end t h y r o x i n e - f e d r e t s w ith s m a ll d o se s o f a l l y l
fo rm a te w hich c a u se d s e ro u s inflem im ation o f th e l i v e r .
H i s t o l o g i c a l i n v e s t i g a t i o n showed t h a t t h e a d m i n i s t r a t i o n o f
t h y r o i d p r e p a r a t i o n s i n t e n s i f i e d th e s e ro u s in fla m m a tio n b u t
a p p a r e n t l y prom oted r e g e n e r a t i o n , w h ile th e l i v e r o f th e
th y r o id e c t o m iz e d a n im als showed th e m ost se v e re d e s t r u c t i o n ,
e s p e c i a l l y e x te n s i v e n e c r o s i s end th e a b sen c e o f any a tte m p t
a t r e g e n e r a t i o n . The t h y r o i d g la n d may, t h e r e f o r e , be
c o n s i d e r e d as p ro m o tin g r e g e n e r a t i o n o f th e l i v e r . From t h i s
ty p e o f work i t may a ro u s e o u r s u s p ic i o n t h a t th e t h y r o i d
g la n d a ls o p ro m o tes th e r e g e n e r a t i o n o f o t h e r t i s s u e s .
Von M o l l e n d o r f f f o u n d t h a t d e s o x y c o r t i c o s t e r o n e
c a u se d an i r r e g u l a r d i s t r i b u t i o n o f th e chromosomes in th e
d a u g h te r c e l l s and a ls o c a u se d th e s p l i t t i n g o f chromosomes
w h ic h , u n d e r c e r t a i n c o n d i t i o n s , co u ld l e a d to d i v i s i o n i n to
^ S p i e s s - B e r t s c h i n g e r (Med. U niv. Wien, Germany),
A r c h , p a t h , a n a t . p h y s i o l . (Virchow* s ) , 3 1 2 :6 0 1 -6 1 5 , 1948.
W, von M o lle n d o rf, H e r, n a t u r f o r s c h . G es. F r e i b u r g
B r e i s g a u , 3 7 :1 8 7 -2 0 2 , 1942. Ghem. Z e n t r . 1942, I I , 7 93-94 .
more th a n two d a u g h te r c e l l s . D e s o x y c o r tI c o s te r o n e produced
t h i s d i s t u r b a n c e in m i t o s i s in a wide c o n c e n t r a t i o n ran g e
th o u g h to a m o d e ra te d e g re e , b u t i t lo w e re d th e r a t e o f
d i v i s i o n in g e n e r a l .
E f f e c t on b a s a l m e t a b o l i c r a t e . According: to D o etsch ,
V e r z a r and W irz^^ a d r e n a le c to m iz e d c a t s r e q u i r e a minimum o f
0 . 8 mg/kg body w e ig h t/d a y o f d e s o x y c o r t i c o s t e r o n e f o r
m a in te n a n c e , b u t i f th e y w ere a ls o th y r o id e c to m iz e d th e y
r e q u i r e d o n ly 0 . 1 - 0 . 2 m g /k g /d a y . A verage oxygen consum ption
o f norm al c a t s i s 803 c o / k g / h r . T his was d e c r e a s e d about
tw e lv e p e r c e n t by th y ro id e c to m y b u t was n o t a f f e c t e d by
a d re n a le c to m y i f d e s o x y c o r t i c o s t e r o n e was g iv e n . In a l l
c a s e s a d m i n i s t r a t i o n o f th y r o x in e i n c r e a s e d oxygen consump­
t i o n . The r e s u l t s o f a n o t h e r e x p erim en t o f th e s e w o rk e rs
a r e summarized a s fo llo w s :
O2 consum ption a t r e s t f o r
i n t a c t r a t s
a d r e n a le c to m iz e d r a t s com pensated w ith
d e s o x y c o r t i c o s t e r o n e 837
th y r o id e c to m iz e d r a t s 373
th y r o id e c to m iz e d and a d re n a le c to m iz e d
r a t s when com pensated w ith
d e s o x y c o r t i c o s t e r o n e 368
A c co rd in g to t h e s e w o rk e rs , ab sen ce o f th e adi-enal m e d u lla
42 R, D o e ts c h , F. V e r z a r and H. W irz, H e lv . P h y s i o l .
Pharma c o l . A c t a , 3 :5 6 5 -8 7 , 1945. H e lv . P h y s i o l . P h a rm a c o l.
A c ta 3 , C 1 8 -1 9 , 1945.
27
d o e s n o t i n f l u e n c e th e b a s a l m e ta b o lic r a t e .
A dren al c o r t e x v e r s u s t h y r o i d g l a n d . R o k h lin a and
S t u d i t 8 k i i 4 3 im p la n te d th e a d r e n a l c o r t e x o f r a t e i n t o
c h o r i o - a l l a n t o l c en v elo p e o f e i g h t - d a y c h ic k embryos and
i n h i b i t e d th e developm ent o f th e t h y r o i d . The i n h i b i t i o n
i s e s p e c i a l l y e v id e n t tw e lv e to f o u r t e e n days a f t e r in c u b a ­
t i o n . M orel and G in e s te ^ ^ fo u n d t h a t r e p e a t e d i m p l a n t a t i o n s
o f a d r e n a l c o r t e x t i s s u e in young r a b b i t s caused some
i n h i b i t i o n o f t h y r o i d s e c r e t i o n . Elmer,45 e t a l found t h a t
d e s o x y c o r t i c o s t e r o n e a lo n e s l i g h t l y s t i m u l a t e d th e t h y r o i d .
43 M, L. R o k h lin a and A. N. S t u d i t s k i i , B u ll b i o l .
m ed. e x p t l . U .R .S .S . 3 :1 7 1 - 4 , 1937.
44 J , M orel and P. J . G in e s te , Compt. r e n d . s o c . b i o l .
1 3 0 :4 6 5 - 7 , 1939*
45 A. W. E lm er, B. G ie d o sz , M. Scheps and H. Weber,
Compt. re n d , s o c . b i o l . , 1 3 1 :2 9 1 -2 , 1939.
CHAPTER I I
EXPERIMENTATION
In o r d e r to be a b le to m easure t h e e x a c t h e i g h t o f
th e t h y r o i d e p it h e l i u m a c c u r a t e l y i t i s n e c e s s a r y to h a n d le
th e t h y r o i d g la n d s c a r e f u l l y to p r e v e n t m a c e r a tio n ,
s h r in k a g e and d i s t o r t i o n o f t h e s e t i s s u e s . This p h a se o f
work in v o lv e d m a in ly th e i n j e c t i o n o f th e r a t s w ith d eso x y ­
c o r t i c o s t e r o n e , th y ro id e c to m y and th e m aking o f s l i d e s .
The p r o p e r t i e s o f d e s o x y c o r t i c o s t e r o n e . T h is hormone
i s i n s o l u b l e i n w a t e r , s p a r i n g l y s o l u b l e in a lc o h o l, a c e to n e ,
d io x a n e end v e g e t a b l e o i l s . I t i s o d o r l e s s and s t a b l e in
a tm o s p h e ric oxygen. I t s m e l t in g p o i n t i s betw een 15 4-160 ^0.
I n j e c t i o n o f d e s o x y c o r t i c o s t e r o n e . The d e s o x y c o r t i ­
c o s t e r o n e u se d f o r th e e x p e rim e n ts was in th e form o f an
a c e t a t e w hich came in c r y s t a l foim and in o i l . The c r y s t a l
form was d i s s o l v e d in sesame o i l w hich was warmed in a w a te r
b a t h to 50-60^C end s t i r r e d w ith a g l a s s r o d to h a s t e n
s o l u t i o n o f th e c r y s t a l s . Enough c r y s t a l s were d i s s o l v e d to
make a c o n c e n t r a t i o n o f f i v e m illig r a m s o f th e hormone in
one c u b ic c e n t i m e t e r o f th e o i l .
The i n t r a m u s c u l a r r o u t e was ch o sen f o r th e i n j e c t i o n
b e c a u s e th e hormone e n t e r s th e b loo d stre a m v e ry slo w ly from
th e s k e l e t a l m u sc le , t h e r e b y giving: a p ro lo n g e d e f f e c t . The
29
s i t e o f i n j e c t i o n was chosen a t th e g l u t e a l r e g i o n . The o i l
was warmed to a b o u t 3?0C j u s t b e fo re i n j e c t i o n to make i t
t h i n n e r and t h e r e f o r e e a s i e r to i n j e c t . A lOcc s y r i n g e and
a 2 2 -g au ge n e e d le were u s e d . The s y r in g e and n e e d le were
b o i l e d in d i s t i l l e d w a te r f o r ab out tw e n ty m in u te s t o k i l l
p a th o g e n ic o rg a n is m s .
The e x p e r im e n ta l a n i m a l s . About s i x t y - f i v e a lb i n o
r a t s w ere u se d f o r th e e x p e rim e n ts i n an a tte m p t to a c h ie v e
more r e p r é s e n t â t iv e and more a c c u r a t e r e s u l t s . Out o f th e s e
o n e - t h i r d s e rv e d as norm al c o n t r o l r a t s w hich r e c e i v e d no
i n j e c t i o n a t a l l . A n o th er o n e - t h i r d w ere i n j e c t e d w i t h 10
mgs. o f hormone p e r k ilo g ra m o f th e body w e ig h t o f t h e r a t s .
The r e s t were i n j e c t e d w i t h 20 mgs. hormone p e r k ilo g ra m
body w e ig h t to se e i f g r e a t e r amount o f hormone i n j e c t e d
w ould e f f e c t th e h e ig h t o f t h y r o i d e p ith e liu m m ore. A p e r io d
o f tim e was a llo w e d to e l a p s e betw een th e i n j e c t i o n o f th e
hormone and th y ro id e c to m y o f th e r a t s . Some r a t s w ere g iv e n
a p e r i o d o f two d a y s , w h ile o t h e r s were g iv e n a p e r i o d o f
t h r e e , f i v e and s i x d a y s . T h is a f f o r d s an o p p o r t u n i t y o f
f i n d i n g o u t i f t h e r e i s a d i f f e r e n t e f f e c t on th e e p it h e l i u m .
A p p ro x im a te ly h a l f o f th e number o f th e r a t s were ira le and
th e o t h e r s fe m a le . About h a l f o f them w ere a p p ro x im a te ly
f o u r to f i v e m onths o ld , w h ile th e r e s t were ab out one and a
h a l f months o ld .
30
T h y ro id e cto m y . The r a t was a n e s t h e t i z e d w i t h e t h e r
and i t s l e g t e s t e d f o r r e f l e x re s p o n s e to p in c h in g . When no
r e s p o n s e c o u ld be e l i c i t e d , th e r a t was p la c e d on i t s back
on a c o rk b o a rd f o r s u r g e r y .
A s t r i n g was t i e d a ro u n d each o f th e f o r e l e g s , and
th e s t r i n g s w ere th e n t i e d t o g e t h e r b e h in d th e b o a rd . The
h in d l e g s were t i e d in th e same m anner. I t s neck was
s t r e t c h e d s l i g h t l y by p u t t i n g a ru b b e r b and around th e f r o n t
t e e t h o f th e u p p e r jaw, p u l l i n g a l i t t l e fo rw ard and th e n
w in d in g arou nd a z o o l o g i c a l n e e d le w hich was s tu c k i n t o th e
b o a r d .
An i n c i s i o n was made a lo n g th e m id - v e n t r a l l i n e of
th e s k in w ith a p a i r o f s c i s s o r s , a n o t h e r one a lo n g th e
m a n d ib le on each s i d e and a n o th e r a lo n g t h e c l a v i c l e on
e i t h e r s i d e . The s k in was r e f l e c t e d and th e f a s c i a c le a n e d
away from th e u n d e r l y i n g m u s c le s . Care was tak en n o t to
r u p t u r e any m a jo r b lo o d v e s s e l s s i n c e t h e r u p t u r e o f su ch a
v e s s e l would f i l l th e re g io n o f th e t h y r o i d g la n d w i t h b lo o d ,
m aking th e o p e r a t i o n d i f f i c u l t and m ig h t k i l l th e r a t . Care
was ta k e n n o t to a llo w th e r a t s to d i e b e f o r e th e t h y r o i d
g la n d s were ta k e n o u t.
W ith a p a i r o f f o r c e p s th e S te rn o h y o id e u s wais p u l l e d
s l i g h t l y to th e s id e and f i x e d w ith a few sm all w ire hooks
a t t a c h e d to r u b b e r bands. T h is exposed th e t h y r o i d g la n d s .
The g la n d s w ere g e n t l y t e a s e d away from th e tr a c h e a w i t h two
31
p a i r s o f f o r c e p s , im m e d ia te ly p la c e d in f i x i n g f l u i d and
num bered f o r th e sake o f i d e n t i f i c a t i o n . The r a t was a f t e r ­
w ards s a c r i f i c e d , w rapped in p a p e r and b u r n e d in an
i n c i n e r a t o r .
The m easurem ent o f th e t h y r o i d e p i t h e l i u m . The
e p it h e l i u m was m easured u n d e r h ig h power o f a m ic ro sc o p e by
means o f an o c c u l a r m ic ro m e te r w hich h as been c a l i b r a t e d
i n t o m icro n s by th e h e lp o f a s ta g e m ic ro m e te r. The f i g u r e s
in t h e t a b l e s a r e g iv e n as th e number o f d i v i s i o n s o f th e
o c c u l a r m ic ro m e te r f o r convenience* s a k e . Each o f th e
d i v i s i o n s i s e q u a l to 3 .2 5 m ic ro n s . T h e r e fo re t h e s e f i g u r e s
m ust be m u l t i p l i e d by 3-25 to g e t th e m easurem ent in m icro n s.
Care was ta k e n to m easure o n ly th e o u t e r and th e i n n e r
o u t l i n e s of th e e p it h e l i u m , and not to i n c lu d e th e i n t e r s t i ­
t i a l c e l l s w hich som etim es l i e c lo s e to th e o u t e r b o rd e r of
th e e p it h e l i u m .
32
The t h y r o i d g la n d Ic made up o f many t i n y f o l l i c l e s
and th e i n t e r s t i t i a l t i s s u e c e l l s . Each f o l l i c l e i s made
up o f an e p ith e liu m ( u s u a l l y o n e - c e l l t h i c k ) w hich c o n t a i n s
a. c o l l o i d . The e p ith e liu m o f many f o l l i c l e s in a t h y r o i d
g la n d i s m e a su re d . An a tt e m p t i s made to m easure th e
e p th e liu m from many d i f f e r e n t p o r t io n s o f th e t h y r o i d g la n d
in o r d e r to g e t a r e p r e s e n t a t i v e a v e ra g e f o r th e g la n d as a.
w h o le . F o r some t h y r o i d g la n d s th e r e a d i n g s were so c o n s t a n t
t h a t o n ly s e v e r a l r e a d in g s w ere deemed n e c e s s a r y . When th e
r e a d i n g s were n o t v e ry c o n s t a n t , a o o u t tw e n ty , t w e n t y - f i v e
o r more f o l l i c l e s w ere m easured u n t i l a r e p r e s e n t a t i v e
a v e ra g e was o b t a i n e d . In t h i s c ase o n ly th e r e p r e s e n t a t i v e
r e a d i n g s t h a t w ould g iv e th e same r e p r e s e n t a t i v e a v e ra g e
w ere g iv e n in t h e t a b l e s .
The making o>f s l i d e s . In o r d e r to k i l l th e t i s s u e s
and y e t keep them in c o n d i t i o n s a s n e a r to th e l i v i n g as
p o s s i b l e th e g la n d s were p u t p ro m p tly i n t o s e v e r a l f i x i n g
f l u i d s recommended by Da Fano, H e n sley , Regaud, Z enker and
H e l ly . The t i s s u e s were th e n washed w i t h w a te r , d e h y d r a te d
in a lc o h o l o f p r o g r e s s i v e l y h i g h e r s t r e n g t h s , c l e a r e d in
x y l e n e , d io x a n e , bergam ot o i l o r c lo v e o i l , i n f i l t r a t e d w ith
t i s s u e mat o f 58^0 m e ltin g p o i n t , and imbedded in th e t i s s u e
mat b l o c k s . The b lo c k s w ere w elded i n t o th e s u r f a c e of
wooden b lo c k s and trimmed f o r s e c t i o n i n g . The b lo c k s w ere
33
th e n s e c t i o n e d , and th e s e c t i o n s were a f f i x e d to th e s l i d e s .
The s e c t i o n s on th e s l i d e s w ere s t a i n e d and m ounted in
n e u t r a l balsam . The p r o c e d u r e s f o r th e m aking o f th e s l i d e s
a r e g iv e n b r i e f l y in th e f o l lo w in g p a g e s .
D i f f e r e n t s t a i n s a r e u se d f o r d i f f e r e n t m ethods o f
f i x i n g t i s s u e s i n o r d e r to g e t b e s t r e s u l t s and to demon­
s t r a t e d i f f e r e n t components o f th e c e l l s . These v a r i o u s
s t a i n s t o g e t h e r w i t h t h e i r fo rm u la s and p r o c e d u r e s f o r
t r e a t i n g th e t i s s u e v / il l be g iv e n in o u t l i n e form in th e
f o l lo w in g p a g e s .
D e la f ie ld * 8 h e m a to x y l i n - e o s in method;
1. f i x t i s s u e in Z enker*s f l u i d 24 hours
2. p u t t i s s u e in ru n n in g w a te r 24 h o u rs
d e h y d ra te in ;
3.
30/ e t h y l a lc o h o l 2 h o urs
4. 50/ e t h y l a lc o h o l 2 hours
5.
70/ e t h y l a lc o h o l 2 h o u rs
6 . 80/ e t h y l a lc o h o l 2 hours
7.
9 5 / e t h y l a lc o h o l 2 h ours
8. a b s o l u t e a lc o h o l 2 ho u rs
9.
a b s o l u t e a lc o h o l
3
h ours
c l e a r in ;
10. ' x y le n e 2 h o urs
11. x y le n e 2 h o urs
12. x y le n e 2 hours
34
i n f i l t r a t e w ith :
1 3 . p a r a f f i n 2 h o u rs
14. p a r a f f i n 2 h o u rs
1 5 . p a r a f f i n 2 h o u rs
1 6 . imbed and tr im th e b lo c k f o r s e c t i o n i n g and
a f f i x i n g s e c t i o n s on s l i d e s .
N ote: I f d io x a n e i s u s e d , o m it a l l th e a l c o h o l s
and t r a n s f e r t i s s u e s d i r e c t l y from r u n n in g w a te r
to d io x a n e . T hree changes o f d io x a n e o f two
h o u rs each a re n e c e s s a r y .
S t a i n i n g p r o c e d u r e s :
1 7 . p a s s s l i d e th r o u g h x y le n e , a b s o l u te a l c o h o l down
th ro u g h p r o g r e s s i v e l y w eak er a lc o h o ls to
d i s t i l l e d w a t e r .
N ote: I f c e l l o i d i n s o l u t i o n i s u s e d , th e s l i d e
may p a s s from x y le n e to th e c e l l o i d i n s o l u t i o n
and th e n from h e r e d i r e c t l y to d i s t i l l e d w a te r .
18. h e m a to x y lin s o l u t i o n few m in u te s
1 9 . d e s t a i n in a c i d - a l c o h o l i f n e c e s s a r y
20. wash in w a te r and th e n in ammonia s o l u t i o n
21. wash a g a in in w a t e r
22. e o s i n few m in u te s
2 3 . d e s t a i n in 7 0 / a l c o h o l i f n e c e s s a r y
24. 9 5 / a lc o h o l
2 5 . a b s o l u t e a lc o h o l
35
26. x y l e n e .
2 7 . mount in balsam w i t h number 1 cover s l i p
S i l v e r method o f Da Fano
1. F ix in Da F a n o *s f l u i d
c o b a l t n l t r a . t e
d i s t i l l e d w a t e r
f o rm a lin
6-8 h o u rs
1 gram
100 cc
15 cc
2. Wash q u ic k ly in aq. d i s t . and im p re g n ate
i n 1 . 5/ s i l v e r n i t r a t e 24-48 h o u rs
3 . Wash r a p i d l y in aq . d i s t . and c u t down
t i s s u e s to 2 mm o r l e s s t h i c k
4. Reduce in O a j a l * s m ix tu re
6 .
7 .
8 .
9 .
1 2 -2 4 ho u rs
uranium n i t r a t e
f o r m a lin
d i s t i l l e d w a t e r
1 gram
15 cc
100 cc
1 /2 hour
2 ho u rs
5 . Wash in d i s t i l l e d w a te r
D e h y d ra te , c l e a r and imbed
P ass s l i d e s th ro u g h x y le n e , a b s o l u t e
a l c o h o l down to w a te r
Gold c h l o r i d e 0 . 1 - 0 . 2 /
C o u n t e r s t a i n w ith alum c arm in e
Al urn c arm in e s t a i n
In 5 / aqueous s o l u t i o n o f NH^ alum
b o i l f o r 10-20 m in u te s 1 / powered c arm in e .
Cool and f i l t e r . T his i s v e ry e asy to use
s in c e i t w i l l n o t o v e r s t a i n .
10. D e h y d ra te , c l e a r , and mount
36
3.
B e n s l e y ' s method
1. F ix in f o llo w in g s o l u t i o n 24 h o u rs
K2Cr20y 2 . 5 / 8 cc
Osmic ex id 2 / 2 cc
G l a c i a l a c e t i c a c id 1 c ro p
2. Wash, d e h y d r a te , c l e a r and imbed; burgam ot o i l
i s u se d i n s t e a d o f x y le n e . S e c tio n s sh o u ld be
as t h i n as 4 m ic ro n s o r l e s s .
P a ss s e c t i o n down to w a te r
4. Dip in 1 / KMnOg
5. R in se in 5 / o x a l i c a c id
Wash in w a te r
S t a i n w ith a n i l i n e f u o h s in
a n i l i n e w a t e r 100 cc
a c i d f u o h s i n 20 g
A n i l i n e w a te r i s made up a s fo llo w s ;
Shake up 4 cc o f a n i l i n e in O Q cc
d i s t i l l e d w a t e r end f i l t e r th e m ix tu re
th r o u g h a w et f i l t e r
Wash r a p i d l y in w a t e r
D i f f e r e n t i a t e in a 1 / aqueous s o l u t i o n o f m eth yl
g re e n
R in se r a p i d l y in 9 5 / a l c o h o l . P ass th r o u g h
s e v e r a l ch an ges o f a b s o l u t e a lc o h o l i n t o
6 .
1 m inu te
1 m inu te
6 m in u te s
7.
8 .
37
x y le n e and mount In b alsam
N ote: N e u tra l balsam o r c e d a r o i l must be
u s e d
Re g a u d ‘ s method
1. F ix t i s s u e s in f o llo w in g s o l u t i o n f o r 4 d a y s ,
c h a n g in g i t e v e ry day
^2^^^2^7 3 / 80 p a r t s
formed in (co m m ercial) 20 p a r t s
2. M ordant in 3 / ^2^^2^7 s o l u t i o n f o r 7 d a y s ,
c h a n g in g e v e ry seco nd day
3. Wash in ru n n in g w a te r f o r 24 h o u rs
4. D e h y d ra te , c l e a r and imbed and c u t t h i n s e c t i o n s
5» Mount and p a s s s e c t i o n s down to w a te r in th e
u s u a l way
6. M ordant in 5 / i r o n alum a t 35^ C f o r 24 h o u rs
7. R in se in d i s t i l l e d w a te r (n o t t a p w a t e r ) . Do
n o t r i n s e to o lo n g b e f o r e s t a i n i n g o r e l s e
m ordant w i l l be washed o f f
8. S t a i n in r i p e n e d h e m a to x y lin (a few weeks o f
r i p e n i n g ) f o r 24 h o u rs
H em atoxylin s t a i n
h e m a to x y lin 1 g
a b s o l u t e a lc o h o l 10 cc
g l y c e r i n 10 cc
d i s t i l l e d w a te r 80 cc
D i s s o lv e h e m a to x y lin in a b s o l u t e a c l o h o l f i r s t ;
38
th e n a.dd g l y c e r i n and w a t e r
9 . D i f f e r e n t i a t e in 5 / ir o n alum , w a tc h in g u n d e r a
m ic ro s c o p e . D e h y d ra te , c l e a r and m ount.
B e n s l e y * s b r a z i 1 in - W a s s e r b lau method
1. Z e n k e r 's f l u i d , l e s s a c e t i c a c i d , p lu s 1 0 /
f o r m a lin 24 h o u rs
2. Wash, d e h y d r a te , c l e a r , imbed end s e c t i o n
3 . P a ss down to w a t e r
4. I o d i z e w ith L u g o l' s s o l u t i o n 30 secon ds
LiUgol's s o l u t i o n
KI 6 g
I 2 4 g
w a te r 100 cc
5 . S t a i n in f o l lo w in g s o l u t i o n s e v e r a l ho u rs
b r a z i l i n 0 .0 5 g D is s o lv e b r a z i l -
d i s t i l l e d w a t e r 100 cc in in w a t e r w ith
p h o s p h o tu n g s tic a c i d 1 g a id o f h e a t
th e n add p h o s­
p h o t u n g s t i c a c i d
N ote: r i p e n i n g may be a c c e l e r a t e d by a d d in g
0 , 4 cc o f h y d ro g en p e r o x id e o r a few d ro p s o f
s o l u b l e m oly b d ic a c i d . T h is s o l u t i o n sh o u ld
n o t be used a f t e r t h r e e d ay s
6. R in se in d i s t i l l e d w^ater
7 . P la c e in f o llo w in g s o l u t i o n
p h o s p h o tu n g s tic a c i d 1 g
w a s s e r b la u 0 . 2 g
d i s t i l l e d w a t e r 100 cc
8. Wash r a p i d l y in d i s t i l l e d w a t e r , d e h y d ra te in

CHAPTER I I I
RESULTS
The norm al c o n t r o l r a t s » A p p ro x im a te ly tw e n ty o r
more r a t s were u s e d as norm al c o n t r o l . Of t h i s number about
o n e - t h i r d were m ale, and th e r e s t w ere fe m a le . The male
r a t s w ere betw een t h r e e and s i x m onths o l d , w h ile t h e fem ale
w ere betw een t h i r t y end f o r t y days o l d . The t o t a l a v e ra g e
h e i g h t o f th e e p it h e l i u m o f t h i s group o f r a t s i s 7 .5
m ic ro n s . The a v e ra g e o f th e young fem ale r a t s i s 6 .3
m ic r o n s , w h ile t h a t o f th e o l d male i s 8 .? m ic ro n s. P l a t e 1
shows th e p i c t u r e s o f th e t h y r o i d g la n d s o f Rat No. 4 and
R at No. 3 0 1 young norm al and o ld norm al r a t s r e s p e c t i v e l y .
The r a t s r e c e i v i ng 10 mgs hormone p er kg body w e i g h t .
T his group o f r a t s was s u b d iv id e d i n t o two age g ro u p s o f
f o u r to f i v e m onths o ld and a b o u t one and a h a l f m onths o ld .
The o l d e r r a t s w ere d iv id e d a g a in i n t o m ale and f e m a l e ,
w h ile th e y o u n g er r a t s w ere a l l fe m a le . In a l l t h e s e r a t s
th e lo w e s t e p it h e l i u m was 9 . 4 2 u , and th e t a l l e s t was 1 5 . cu
w i t h a t o t a l a v e ra g e o f 1 1 . 3 4 u . T his means t h a t th e t o t a l
a v e r a g e i s 3*54 m ic ro n s g r e a t e r than t h a t o f th e norm al
(1 1 .3 4 m icro n s m inus 7 .8 m ic r o n s ) . See T ables 1 and 4.
The young fem ale r a t s r e c e i v i n g 10 mgs o f hormone a.s
compared w ith th e young fe m a le norm al c o n t r o l ra.ts had t h e i r
41
e p it h e l i u m th ic k e n e d to 1 1 .0 8 m ic ro n s, 4 ,7 7 m ic ro n s l a r g e r
th e n th e young norm al fem ale e p ith e liu m (se e T a b le s 2 and
7 ) . The e p it h e l i u m o f th e o l d fem ale r a t s r e c e i v i n g 10 mgs
o f hormone i s 0 ,8 2 m icro n s t a l l e r th a n t h a t o f t h e young
fe m a le r a t s r e c e i v i n g th e same amount o f hormone (se e T ables
5 and ? )• The e p ith e liu m o f th e o ld m ale r a t s w hich to o k
10 mgs o f hormone was t a l l e r th a n th e o l d fem ale r a t s which
r e c e i v e d th e same q u a n t i t y o f horm one. I f th e s e r e s u l t s a re
v a l i d , t h e r e i s a sex d i f f e r e n c e in t h e a c t i o n o f th e
hormone on th e e p i t h e l i u m , th o u g h i t i s v e ry s l i g h t . See
T a b le s 5 and 6, and a ls o P l a t e s 3b and 4b. These r e s u l t s a re
p r e s e n t e d g r a p h i c a l l y on Graphs 1 and 2.
The r a t s r e c e i v i n g 20 m gs/kg o f horm one. T h is group
o f r a t s was s u b d iv id e d i n to two g ro u p s, young fem a le and o ld
m a le . In a l l t h e s e r a t s t h e lo w e s t e p it h e l i u m was 6 .5 u , and
th e t a l l e s t was 1 4 . 97u w i t h a t o t a l a v e r a g e o f 1 0 . 7 3 u , which
was 2 ,9 3 m icro n s g r e a t e r th a n th e t o t a l a v e ra g e h e i g h t of
th e e p ith e liu m o f th e norm al c o n t r o l r a t s , but O .o l m icrons
l e s s th a n th e a v e ra g e h e ig h t of th e e p it h e l i u m of t h e r a t s
w h ich r e c e i v e d o n ly 10 m gs/kg horm one. These r e s u l t s
i n d i c a t e t h a t t h e r e i s a d i f f e r e n c e in r e s p o n s e o f th e
e p ith eliiu m to th e amount o f th e hormone r e c e i v e d by th e r a t s .
The hormone i s p r o b a b ly t o x i c when g iv e n in l a r g e r d o s e s .
See T ab les 1, 4 and 8 f o r th e r e s u l t s . See P l a t e s l b , 6b,
42
and 8b.
The e p i t h e l i u m o f th e young fe m a le r a t s o f t h i s group
was a ls o l e s s t a l l th en th e young fem a le r a t s w hich r e c e i v e d
o n ly 10 m gs/kg hormone, th e d i f f e r e n c e b e in g 0 .42 m ic r o n s .
I t i s s t i l l l e s s t a l l th a n th e o ld fe m a le r a t s r e c e i v i n g
10 m gs/kg horm one. See T a b le s 5> 7 and The e p it h e l i u m o f
th e o l d male r a t s o f t h i s g ro u p i s o n ly a b o u t 0 .1 3 m ic ro n s
l e s s th a n t h a t o f th e o ld m ale r a t s w h ich r e c e i v e d o n ly 10
m gs/kg horm one. See T a o le s 6 and 10. See a ls o P l a t e s l a ,
3a and ?a f o r t h e r e s u l t s o b t a i n e d from th e fem ale r a t s and
P l a t e s l b , 6b and 7b f o r th o s e o b ta in e d from th e m ale r a t s .
The i n f l u e n c e o f age on th e h e i g h t of e p i t h e l i u m . As
h a s been m e n tio n e d , t h e r e i s a d i f f e r e n c e in th e h e i g h t o f
th e e p ith e liu m a c c o rd in g to a g e . In th e norm al c o n t r o l r a t s
th e a v erag e t h y r o i d e p it h e l i u m o f th e o l d e r ones i s 2 .4 0
m ic ro n s t a l l e r th a n t h a t o f t h e younger o n e s . A l e s s p r o ­
nounced d i f f e r e n c e was n o t i c e d in th e g ro u p o f r a t s w hich
r e c e i v e d 20 m gs/kg hormone, th e d i f f e r e n c e b e in g 1 .2 4
m ic r o n s . The l e a s t p ro n o u n ced was o b s e rv e d in th e group
w hich r e c e i v e d o n ly 10 m gs/kg hormone, th e d i f f e r e n c e h e re
b e in g o n ly 0 .8 8 m ic ro n s o b t a i n e d by s u b t r a c t i n g th e a v e ra g e
h e i g h t o f th e young e p it h e l i u m from t h a t o f th e e p it h e liu m
o f a l l th e r a t s o f t h i s g ro u p . See T a b le s 1 to 8.
The i n f l u e n c e o f se x . S ince w i t h i n th e sane age
43
g ro u p t h e r e were no m ales and fem ales to compare, i t i s not
p o s s i b l e to s t a t e i f t h e r e i s a d i f f e r e n c e in th e h e i g h t o f
th e e p ith e liu m betw een th e two s e x e s . T h is i s t r u e o f th e
g ro u p o f r a t s w hich se rv e d as norm al c o n t r o l and a l s o o f th e
g ro u p o f r a t s w h ich r e c e i v e d 20 m gs/kg hormone. F o r t u n a t e l y ,
in t h e same gro up o f r a t s t h a t r e c e i v e d 10 m gs/kg hormone i t
was p o s s i b l e to n o te th e i n f l u e n c e t h a t sex may have on th e
a c t i o n o f th e hormone on t h e h e ig h t o f th e e p it h e l i u m even
th o u g h th e r e s p o n s e o f th e e p it h e l i u m was s l i g h t . In t h i s
g ro u p o f r e t s t h a t r e c e i v e d 10 m gs/kg o f hormone th e o ld
m ale r a t s have t a l l e r e p it h e l i u m th a n t h e o ld fem ale r a t s ,
th e d i f f e r e n c e b e in g 0 .1 3 m ic ro n s . See T ab les 5 and 6 and
Graph 2a.
The i n f l u e n c e of th e t ime e le m e n t . In a. g ro u p o f
a b o u t tw e n ty norm al c o n t r o l r a t s th e h e i g h t o f th e t h y r o i d
e p it h e l i u m v a r i e s betw een 4 .8 u and 1 2 .6 ? u w ith a t o t a l
a v e r a g e o f ? .8 u . A n o th er g ro u p o f tw e n ty -o n e r a t s w ere
i n j e c t e d w ith 10 m gs/kg hormone - and w ere s a c r i f i c e d on
d i f f e r e n t d a y s, f i v e o f them two days a f t e r i n j e c t i o n , f i v e
t h r e e days a f t e r i n j e c t i o n and e le v e n f i v e days l a t e r . The
e p t h e l i e l heig'ht o f • th e r a t s s a c r i f i c e d two days a f t e r w a r d s
v a r i e s betw een 9 . 40u and 1 5 .6 0 u w ith a t o t a l a v e ra g e o f
1 2 . 94u. That o f th e r a t s s a c r i f i c e d t h r e e days a f t e r v a r i e s
betw een 9-75u and 1 3 .80u w i t h a t o t a l a v e ra g e o f 1 1 .2 1 u .
44
Those t h a t w ere k i l l e d f i v e da.ys a f t e r lia.d th e h e i g h t d i f f e r ­
ing: betw een 9-40u and l ^ .l O u w ith a t o t a l a v erag e o f 1 0 .9 5 u .
From t h e s e e x p e rim e n ts i t i s o b se rv e d t h a t th e a c t i o n o f th e
hormone on th e e p ith e liu m wa.s a t i t s h e i g h t two day s a f t e r
i n j e c t i o n and th e n d e c l i n e d t h r e e and f i v e days a f t e r
i n j e c t i o n . See T ab les 11 to 16 and Graph 3*
A group o f f o u r t e e n r a t s were i n j e c t e d w ith 20 m gs/kg
horm one. Three o f them w hich were s a c r i f i c e d two days a f t e r
i n j e c t i o n had e p i t h e l i a l h e i g h t v a ry in g betw een 9«10u and
13'OOu w ith a t o t a l a v e ra g e o f l l . l 4 u . A n o th er t h r e e were
k i l l e d t h r e e d ay s a f t e r w a r d s . The e p i t h e l i a l h e ig h t v a r i e s
from 6 . 5OU to 13»9?u w i t h a t o t a l a v e ra g e o f 1 0 .7 3 u . The
t h i r d grou p o f e i g h t r a t s w ere th y r o id e c to m iz e d s i x days
a f t e r i n j e c t i o n . The e p i t h e l i a l h e ig h t d i f f e r s betw een
9 . 42u end 1 2 ,6 7 u w ith a t o t a l a v e ra g e o f 1 0 .6 6 u . From th e s e
e x p e rim e n ts i t i s a g a in n o t i c e d t h a t th e a c t i o n o f th e
hormone on t h e e p i t h e l i a l h e i g h t was th e g r e a t e s t two days
a f t e r i n j e c t i o n and d e c l i n e d p r o g r e s s i v e l y t h r e e and s i x
d a y s a f t e r .
Summary. The f o l lo w in g r e p r e s e n t s th e o b s e rv e d
e x p e r im e n ta l d a t a :
1. In t h e norm al c o n t r o l r a t s t h e lo w e st e p it h e l i u m
was 4 .8 0 u , and th e t a l l e s t was 12 .6 7 u w i t h a.
t o t a l a v e ra g e o f 7»80u.
45
2 . In th e r a t s i n j e c t e d w ith 10 m gs/kg hormone th e
lo w e s t e p it h e l i u m was 9 . 40u w h ile th e t a l l e s t
was 1 5 . oOu w i t h a t o t a l a v e ra g e of 1 1 . 3 4 u .
3. In th e r a t s i n j e c t e d w ith 20 m gs/kg hormone th e
lo w e s t e p it h e l i u m was 6 .5 0 u end th e t a l l e s t was
1 3 - 97u w ith a t o t a l a v e ra g e o f 10.73%.
4. The lo w e s t e p i t h e l i u m o f f i v e r e t s i n j e c t e d w ith
10 m gs/kg hormone and th y r o id e c to m iz e d two days
a f t e r th e i n j e c t i o n was 9«40u and th e t a l l e s t
was 1 5 . 60u w i t h a t o t a l a v e ra g e o f 1 2 . 94u.
5. The lo w e s t e p it h e l i u m o f a n o th e r f i v e r a t s
i n j e c t e d w i t h 10 m gs/kg hormone and t h y r o i d e c ­
to m iz ed t h r e e days a f t e r th e i n j e c t i o n was 9.75%,
and th e t a l l e s t was 1 3 .80u w i t h a t o t a l a v erag e
o f 1 1 . 2 1 U .
6. The lo w e s t e p it h e l i u m o f e le v e n r a t s i n j e c t e d
w i t h 10 m gs/kg hormone and t h y r o id e c to m iz e d
f i v e days a f t e r th e i n j e c t i o n was 9 .4 0 u , and
th e t a l l e s t was 1 3 *30% w i t h a t o t a l a v e ra g e of
10.95%.
7. In a. group o f e le v e n f o u r - t o - f i v e - m o n t h - o l d r a t s
i n j e c t e d w ith 10 m gs/kg hormone th e t o t a l
a v e ra g e e p i t h e l i a l h e ig h t o f f o u r fem a le r a t s
was 1 1 . 9 Û U , and t h a t o f se v en m ale r a t s was
1 2 . 0 3 % .
46
8. In th e norm al c o n t r o l r a t s th e t o t a l a v e ra g e
e p i t h e l i a l h e i g h t o f o n e - a n d - a - h e l f - m o n t h - o ld
r a t s was 6 .3 1 u , and t h a t o f f o u r to f i v e month
* o l d r a t s was 8 .7 1 u .
C o n c lu s io n s . On th e b a s i s o f t h e s e d a t a , i t i s
t h e r e f o r e c o n c lu d e d t h a t :
a. th e e p ith e liu m o f th e i n j e c t e d r a t s i s t a l l e r th a n
t h a t o f th e norm al c o n t r o l s , but t h a t o f th e
r a t s i n j e c t e d w i t h 20 m gs/kg hormone was low er
th a n t h a t o f t h e r a t s i n j e c t e d w ith 10 m gs/kg
hormone (se e d a ta 1 - 3 ) . T h is m ight be due to
th e f a c t t h a t l a r g e d o se s a r e i n c r e a s i n g l y t o x i c
to th e r a t s ;
b. th e a c t i o n o f th e hormone on t h e e p ith e liu m was a t
i t s h e ig h t two days a f t e r t h e i n j e c t i o n a.nd
d e c l i n e d t h r e e and f i v e d a y s a f t e r th e I n j e c t i o n
( s e e d a t a 4 - 6 ) . T h is phenomenon was a.lso
o b s e rv e d in th e r a t s i n j e c t e d w i t h 20 m gs/kg
hormone ;
c. t h e a c t i o n o f t h e hormone on th e e p ith e liu m was
m o d if ie d by sex s in c e th e t o t a l a v e ra g e
e p it h e l i u m o f th e male r a t s was s l i g h t l y h ig h e r
th a n t h a t o f t h e fem ale (s e e d a t a 7 ) ;
d. th e age o f th e r a t s e x e r t e d some i n f l u e n c e on t h e i r
e p i t h e l i a l h e i g h t (se e d a t a 8 ) .
47
From a l l t h e s e e x p e r im e n ts i t i s o n ly p o s s i b l e to
c o n c lu d e t h a t d e s o x y c o r t i c o s t e r o n e d e f i n i t e l y i n c r e a s e s th e
h e i g h t o f th e norm al t h y r o i d e p it h e l i u m . I t i s n o t p o s s i b l e
to c o n c lu d e d e f i n i t e l y a,t t h i s tim e t h a t t h e age and se x of
t h e r a t s and t h e tim e b etw een th e i n j e c t i o n and t h e t h y r o i d ­
ectom y o f t h e s e anim ads i n f l u e n c e th e a c t i o n o f t h e hormone
on t h e e p i t h e l i a l h e i g h t s i n c e th e number o f a n im a ls u se d
was to o s m a ll.
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TABLE I I
RESULTS ÜBTAILLL B'ROM YüUUÜ- EEI^IALE LûPJlAL CONTROL RATS
R ats No. Age in Months Sex H e ig h t o f E p ith e tlim n
Average
36
l i ?
2 .0 X 3 .2 5 vM .
37 1* 1 .5 X
3 .2 5 M-
39 l i
?
2 .0 X 3 .2 5
AL
40
l i
1 .8 X
3 .2 5
56
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2 .0 X
3 .2 5
M'
57 l i
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M'
58
It-
2 .0 X
3 .2 5
M'
61
1#
1 .6 X 3 .2 5
62
I t
2 .6 X
3 .2 5 AL
To t ah
1 7 .5
X
3 .2 5 A u
T o ta l A verage 1 .9 4 X
3 .2 5
M-
= 6 .3 1 yL L
50
TABLE I I I
RESULTS OBTAINED FROM OLD MALE N0RI4AL CONTROL RATS
Average H e ig h t o f
E p ith e liu m
Age in Months Sex R ats No.
28
T o ta l A verage 2 .68 X 3 • 25
= 8 . 7 1 ^
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" !
52
TABLE V
OLD FEivIALE RATS WHICH RECEIVED 10 MGS HORi-lONE/KG WT.
R a ts No. Age in Months Sex Average H e ig h t o f
K p ith e l liim
6 4-5
4 .0 X 3.25>n.
7 4-5
$
4 .2 5 X 3 .2 5 XL
8
4-5 3 .3 X 3 .2 5 / /.
12
4— 5
?■
3 .0 X 3.25x4,
Tote
rl 1 4 .5 5 X 3 .2 5 /1
T o ta l A verage 3 . 66 3*25>tL
= 11 .9 0 yU.
53
TAiBLE VI
OLD MALE HATS WHICH RECEIVED 10 MG-S/KG WT.
R ats No. Age in Months Sex A verage H e ig h t o f
S p i t h e l l u m
9 4-5
/
3 .0 X 3 . 2 5 / l
10
4— 5
/
3 .0 X 3 . 2 5 / l
16
4-5
/
3 .5 X 3 . 2 5 / c
17 4— 5
/
4. 8 X 3 • 25 >L
18
4— 5 4 .0 X 3 . 2 5 / u
19 4— 5 2 .9 X 3 . 2 5 / l
20
4-5
4 .7 X 3 . 2 5 / l
T o ta l 2 5 .9 X 3.25ylL
T o ta l A verage 3*70 A 3 • 25
1 2 . 0 3
54-
table V II
YüUNÜ- FLÎ-IALE HATS VHICH RECEIVED 10 MGS/KG BODY WEIGHT
R a t8 No. Age in Months Sex Average
E p it
H e ig h t o f
h e liu m
31 1* 3 .1
X
3 ■ ?-5 /L
32
1*
^ J
3 .2 X 3 . 2 5 /L
33 I t
?
3 .2 K
3 . 2 5 / l
34
l i
4.1
X
3 . 2 5 / c
35 1-1
3 .0
X 3 .2 5 > u
41
I t 3 .9 X 3 . 2 5 /L
42
l i 3 .3 X 3 .2 5 /L
43 I t
$
3 .9
X 3 .2 5 /0 .
44
I t
?
3 .5 X 3 .2 5 AL
45 I t
$
2 .9 X 3 .2 5 /U.
Tote 1 3 4 .1 X
3 . 25 jjl.
T o ta l Aver ege 3 .4 1
X 3 .2 5 /L
= 1 1.08 / L
E h
%
M
'U
; h
n
o
n o
U h
O
c b
‘ U
M
M :_ 0
g a
o
lu ru
.-1
m
<
b H
:u
b
o
C x !
ru
M
O
O Î
b q
o
■ — '
zi
• f H
rH
C D
( H
O
• H
(D
> ~ f '\
c - - . :
ru
X
W
•H
q -i
O
C L
C D
lU
I % zq
U -:
i (D t H
j > ( L
I .-f* *1 ^
V t
rH
J I —!
rH
o
rH
•rA
' J I '-n
-U
Cm
I----\
1 %
U v
0 0
C O
O J C H '
■l:-h u
■:J: O
C O
I I \r >
CO
C O
C O
vw
v rv j
I
œ
I.; O
Z J
O
o
o
■ > n
uu
■ C 'i
u 'U
- f U
O
ro
rH
- U
b''
J
0 »
cuK ^'J
^ J U
C ^ i
V O
cu
> 4 U
CO
C O
cv
o J m
t4 C > i
-n
n
c \;
vr
rH
(T \
U -
C H
U U
C “ \
\ -U
O
■uH
O
Cr-
(V
("U
C ^\
c u
c u
I — 1
C "\
( H
C U
(H :
C '\
r H
C \
v u
CU
C " ,
( U
CO
« 4 .1
1 — I
C \
v u
H v u
VO
H -
4
H
10
II
U \
u
c ,
c ''i
C'A
CU
v U
«4 4
>-U
C ^ A
( T \
C D
I — I
IE
4->
O
U A
c -
o
rH
56
TABLE IX
YOUNG FmALE RATS WHICH RECEIVED 20 MGS/KG BODY WEIGHT
R a ts No. Age in Months Sex Average H e ig h t of
E p ith e liu m
46
l i
%
3 .9
X 3.25XA.
47
1-1
%
3 . 4 X 3.25/*,
49 I t
%
3 .2
X 3 .2 5 XL
50 I t
$
3 .7 X 3 . 2 5 / / ,
51 I t
%
3 .0
X 3 .2 5 / /.
52
1*
%
3 .0
X
3 . 2 5 / ,.
53 I t
%
2 .9 X 3 . 2 5 / /
54
I t
%
3 .1 X 3 . 2 5 / /
Tot a l 2 6 .2
X
3 .2 5 /1 ,
T o ta l A verage 3 « 28
X 3 .2 5 /* .
- 10 .6 6 /jL,
57
TABLE X
OLD MALE RATS WHICH RECEIVED 20 MGS HORMONE/KG BODY WEIGHT
R e ts No. Age in Months Sex A verage H e ig h t of
E p ith e liu m
13 4-5
4 .3 X
3 . 2 5 / c
14
4-5
< r
3 .7 X 3 . 2 5 / 1
21
4-5
U.O n
3 . 2 5 m.
22
4— 5
(T
3 .5 X 3 . 2 5 m.
23
Au-5
c /'
2 .8 X
3 . 2 5 / l
Tot e l 1 8 .3
3 . 2 5 m .
T o ta l A verage 3» 66
3 .2 5 m -
= 1 1 . 9 0 j u u
58
T a b l e x i
RATS REC EIV IN G 10 MGS H0H170NE PER KG BODY WEIGHT
R ats No.
Age in
Months Sex
No. o f Days
Between
I n j e c t i o n and
T h yroid ectom y
A verage H eig h t
o f E p ith e liu m
X 3 .2 5 AL
16
4-5
/
2
3 .5
17 4— 5
2 4 .8
18
5
f
2 4 .0
19 4-5
2
2 .9
20 4-5
2
4 .7
To-
bad 1 9 .9
T o ta l Average 3 -9 8
= 1 2 .9 4
59
TABLE X II
RATS RECEIVIMÜ- 20 MGS/KG HOHLONE
R ats No.
Age in
Months 3ex
No. o f Days
Between
I n j e c t i o n and
T h y ro id ecto m y
A verage H eight
o f E o ith e liu m
X 3 . 2 5 /A
21
4-5
2 4 .0
22 4-5
/
2
3 .5
23
4-5 2 2 .8
T o ta l 1 0 .3
T o ta l A verage 3 .4 3
= 1 1 .1 4 M-
60
TABLE X I I I
RATS RECEIVING 10 MGS/KG HORMONE
R a ts No.
Age i n
Months Sex
No. o f Days
Between
I n j e c t i o n a.nd
T h yroidectom y
A verage H eight
o f E p ith e liu m
X 3 . 2 5 / l.
6
4-5
?•
3
4 .0
7 4— 5 3 4 .2 5
8
4— 5 f . 3 3 .3
9 4— 5 3
3 .0
10 4— 5 3
3 .0
Te t a l 1 7 .2 5
T o ta l A verage 3*45
= 11.21 / /
TABLE XIV
RATS RECEIVING 20 MGS/KG HORMONE
61
Rats No.
Age in
Months Sex
No. of Days
Between
Injection and
Thyroidectomy
Average Height
of Epithelium
X 3.25>l
11 4—5
? 3
2.0
13 4-5 3 4.3
14
4-5 3 3.7
To1:al 10.0
Total Average 3*3
= 10.73yW
TABLE XV
RATS liEGEIVING 10 MGS/KG HORiiONE
R a ts No.
Age in
Months Sex
No. o f Days
Between
I n j e c t i o n and
Thyro i d e o t orn y
Av e ra g e He ig h t
o f E p ith e liu m
X 3 .2 5 /L
12 4— 5
?
5
3 .0
31 I t
?
5 3 .1
32
l î
?
5
3 .2
33 l i
$
5
3 .2
34
itf 5
4 .1
33 I s
9-
5
3 .0
41
I t
?
5 3 .9
42
IS
?
5 3 .3
43 I t
?■
5 3 .9
44
l i ­
?
5 3 .5
45 l t
?•
5 2 .9
To't a l 3 7 .1
T o ta l
3 .3 7
= 1 0 .9 5 >4
NOTE: With R at No, 12, w h ich was o ld f e m a le , th e t o t a l
a v e r a g e i s 1 1 . 05>it.
6 3
TABLE XVI
RATS RECEIVING 20 MGS/KG HORITON]
R e ts No.
Age in
Months Sex
No. o f Days
Between
I n j e c t i o n and
Til y ro id e c to m y
A verage H eight
o f E p ith e liu m
X 3 . 2 5 a
46
1*
%
6
3 .9
47 I t %
6 3 . 4
49 I t %
6 3 .2
50
1*
%
6
3 .7
51 l i ?
6 3 .0
52 I t
?
6 3 .0
53 I t
% ■
6
2 .9
54
1*
6
3 .1
Tot:al 2 6 ,2
T o ta l Average 3-28
= 1 0 . 6 6 / a-
G R A P H 1
b4
1 2 . 0 3 - u
1 . 0 3 M-
\O n 3 p .
10- ^C >
ii.q o /L
6 '3 I M
Y
A ll normol control ro ts
Young femole normal control rots
Old mole normol control rots
All rots receiving 10mgs
hormone per kg body Weight
Old (emûle rots receiving
1 0 mgs / kg hormone.
OU mole rats receiv/ng
10 m g s/k g hormone.
Young female rots receiving
1 0 mgs / K g hormone
All rots receiving 2 0 mgs
hormone per kg body weight
Young female rots receiving
2 0 m gs/kg hormone
O l d m o l e r a t s r e c e i v i n g
2 0 m g s / k g h o r m o n e
0 Z 4 6 8 / o f 4
A v e r a g e H e i g h t o f E p i t h e l i u m i n M i c r o n s
gJlAL
12,03/L
U .q o /c
b5
G R A P H 2
A
Old male normal control r o ts
Old male r a ts receiving
10m gs/kg horm one
Old fem ale rats receiving
lO m gs/kg hormone
0 ^ 4 6 8 10 14-
A verage H eight o f E pithelium in M icro n s
B
63lyvL
S n i/A .
lUOd/x
Young fe m a le normof control rats
Old m ale normal control rats
Old fem ale v a ts receiving
10 mgs / tg hormone
Y>ung female rats receiving
lOmgs/kg hormone
o 2 4 6 8 % o 12 (4
Average Height o f Epithelium in M icron s
66
G R A P H 3
a.
L U
AJ
_c
C r >
cn
No. o f doy$ betw een injection and tbyroidecfcomy
67
PLATE 1
A. R at # 4 N orm al, Young Fem ale
B. Rat #30 Old Normal Me.le
6 8
PLATE 2
y #
»
A. R at #37 Young Normal Female
B. R at #0 Normal
69
PLATE 3
A. Rat #43 Young Fem ale R e c e iv in g 10 mg/kg Hormone
B. R at # 8 O ld F em ale R e c e iv in g 10 m g/kg Hormone
70
PLATE k
A. Rat #32 Young Fem ale R eceiv in g 10 mg/kg Rormone
:
,t' L
B . R at^ #17 O ld H a le R e c e iv in g 10 m g/kg H oÆ one
PLATE 5
71
^vv:ar
A. R at"756 Young Fem ale R e c e iv in g 10 m g/kg^orm one
> T ’f X'C">7 '
' r' V ' ^ 0 ' \
B. R a ^ # 1 2 O ld M ale R e c e iv in g 1 0 m g/kg HoTmnone
72
PLATE 6
A. Rat 1P34 ïou n g Female R e c e iv in g 10 mg/kg Hormone
«
%
B.
Old M ale R e c e iv in g 10 m g/kg H o S p n e
73
PLATE 7
A. Rat #53 Young Female R e c eiv in g 20 mg/kg hormone
m
$
B . R at # 1 3 O ld M ale R e c e iv in g 20 m g/kg Honnone
74-
p l a t e 8
c
%»
A. Hat 32 Young Fem ale R e c e iv in g 20 mg/kg Hormone
T',v? \
B. R at # 2 2 Old M ale R e c e iv in g 20 m g/kg Hormone
7 5
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Creator Wong, Kah-King (author) 
Core Title The effect of desoxycorticosterone on the height of normal thyroid epithelium 
Degree Master of Science 
Publisher University of Southern California (original), University of Southern California. Libraries (digital) 
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