Pregnant mare's serum gonadotropin: V. Indomethacin or cort isone and the reversal of antiferility eff icacy of pregnant mare's serum gonadotropin

NTR

P ~ 'S S~RU~ " N " PI~:V.I OR RTISO~ A ~ T ~ ERSALOF A~I E ~ IC OF 'S ~~;UM GO

E

ION

THACIN ~ILITY TROPI!~*

Tarun Gupta a ar

atterjee

partment of P h y s l o l o g y , Raja Peary ~ h a n . . a .~ Hoogh . . . i y ~ ~ st Benga ! 71 ~...... Ut t a r par 25 S,,

liege,

ABS?~ A Pregnant 's sezum gonadotropln ....( G) of IO IU on day 5 of pregna induced luteal d e and equently an absolute re so ptlon of fe.... tunes placentae r e s u l t e d on J n da y 16 Of pregnancy. Simultaneous tee of G a t ~ c l n or isone was f o u ~ to ~ consistentiy effective In ~ e v e n t i ~ t luteolyt~c effect of G. T ~ gro~th of the fetusess placentae as well as corpora lutea was f o u ~ to ....be . le] to controls+ Siml larly, shorteslng of t ~ of pseuCopregnancy £o i0-12 the bilateral !y h y s ~ z e c t o m l z e d rat by and its rata inlng the normal duration of I 20 days in the presence of ~ ~ o thacln tempt us to propose that the P uce4 luteolysls is sslbly reflected through the release 0 f ..... pro s t ag I a~ i

Accepted

a t t he ova r t an leve I . . . . . . .

r publication

~W

May

i,

1978

Delhi.

JUNE 1 9 7 8 VOL. i 7 NO' 6

547

CONTRAC

I

~TION

I

..........

Slnce t ~ d i s c o v e r y o f t ~ a n t l f e r t i l l ty ef feet o f p ~ e g n a n t ' s ser~ { SG) ~ have b e e n incllned to explo the of act of this o a n d e x p e r i e n c e d its s ~ c f eo ic ~e icacy rats (1,2). R e c e n t l y Chatterjee .....Z.... a~/l.(3) have shown tha t ~ ant i fertl I e f feet o f is a p p a r e n t [y re f iected % ~ o u g h duai o v a r i a n hange s o f po !yfol 1 ~ ¢u logene s s..... demise. I t has been d o ~ e d ...... sensitization of ...ovar .. i an fol I i¢ leg wl t h the G ¢ou Id lead to st !mu I at ion o a ppre o lab le y £ e ....(4) ... and ..... an e s t r o g e n p o s s l b l y l ~ u c e s luteal .... ssion ....ith c o r r e s p o ~ i n g d e f i c l e n c of ... ~.o g e s t e ~ n e as evldent In the mat (5) e ~ .....{ 6 ) , ...cow ( 7 ) m o n k e y (8),~and i n the ... human ( 9 } . High ..t o f estro-~ gen on t ~ .....o t ~ r hand, has been doc ~ e d t o have a s t i m u l a t o r y a c t l o n on t p g n a n t ........ .. s ..to ...... size and .......1 p~staqlandln F2a (i0), w h i c h in turn ...leads . to p r e m a t u r e stage of ~n a v a r i e t y of !abo tozy an reals (Ii,12~13)' In thls paper ex Imenta! .....¢.... arl [catlon is made that t ~ P induced pregnancy t e r m l n a t i o n is ~ s s l b l y caused t h r o u g h st I iatlon of as tagl in ...(.~ ) a t t ~ ovBrian ie~l. ..... .......

!

~

..

b o r a t o r y b ~ d .....nuliiParous a i b l n o ~rats ~ g Ze housed .. r cant fled ....s c ~ d u l e ...o£ .. 12 light, a ~ had 6roe access to £oOd ...pellets ..... a .... R e g u l a r l y cycilc we=e made p r e g n a n t ...t..~ o u g h fertiie t%ng with ...... of.....s ~ r m - ~ s l t..l...... vag%na~~ s a r ... . . r.e l.i .b l.e males . T ~ ~ ca7 was ....... d e s l g.n.a.t.e.d. as d a y .... .... into gro~ups as ~ r

ted b y ~ ~ r i n g AG, Germany, was .... I s s o ! v e d i n 0.9~< G a l l a ~ ~injected~ sc a t a ...dose . o f I0 IU (0,2 ml) o n d a y 5 of egnancy. .....!nd .... thacln ( i ~ o c l n ) , ~n lls~d Inhlbltor Of Synt~taSe (14)i d o n a t e d by ~ r c k Insti, te for T h e r a ~ u t i s e a r c h , NeW U.$. A. was so Ived ....i6 ... ¢o=n ....oil .. .... and .... s¢ a t .a ..... ~dose 2.5 ..... kg as per ...t..h e t r e a t nt (Table). sane a c e t a t e (Glaxo o I~ ~d. ) o f 1 . 0 .. t' / 6 a 7 was s ¢ ~ led a stated n . t ~ ..... hie. .......... ..... . .. .. ..............

D~~ss at~nt

on

absolute

of

¢o=

z

fetuses

5

at

placentae

pregnancy .. f o u n d day 16. ... T ~

...t o .....

s

h.s been

that

eo

.... an i g h t :~

(P
JUNE ! 978 ~VOLi 17,~NO. 6

i)

4~

P

< 0

C Z

-

-

-

;

7

:

¸

~

:

~

.

.

.

.

~

*

~

~

~ r - ~ - % ~ - -

~

~

+

C.L. = Corpus luteum.

~SG(I~ay5)

~

.

.

.

72

78

56 0

sacrifice(Day 16)

~o.of v~able fetuses at

.

(P
~

~

~

-

-

~

~

~

_

_

87.8

93.6

95.2 0

r~te (%)

Fetal survival

-

4.4~o.I

5.0 + 0.2

(P< o.ooi

(P< o.oo~) 97.1 ~ 4.8

2.1 _+0.I

4.3 + 0.2

~

ttean C. L wt (rag + SE)

92.0 ~ 6.3

64.8 + 3.2

~ean ovarian ~ (~g + 8E)

* Animals were sacrificed onday 16 of pregnancy.

"

289.5 + 5.9

309.4 + 13.9

Resozbed

303.1 _+8.7

,~an placental wt (rag + SE)

~b. of ImpJanted sites at lapa:rotomy (Day 8)

~C-~--~

82

'

Cortisone(Days 5-15)

~

86

m

P,~SG(Day 5) + Indocin(Days 5,7,9)

W

278.3 + 4.8

281.9 + 8.0

Resorbed

267.6 _+6.7

Mean fetal wt (rag _+~ )

60 &3

"

I0

lO

9

6

No. of animals used

( ~ o c t n ) or cortisone *

~gnancy intenuption by P~&Y3and Its p~ventlon by l~o~thacln

Control P,','iG(~ay 5)

of pregnancy)

Treatment (Day

-

Cortisone (Days 5-15 )

P~SG(Day5) + Indocin(Days° 5,7,9) PMSG(Day5) ÷

P~SG(Day 5~,

Control

Treatment (Day of p~egnancy)

TAB~;

_

M

8

rising e s t r o g e n level c o r r e s p o ~ I n g w % t h a f a i l i n g p r o g e s t e r o n e level is kn n to p r o v i d e a st lmulus for the release of p r o s t a g l a ~ i n P~ (16~17). T abortifacient effect of p st a g l a ~ i n F2a (PGF2a) has en I I docu n d In a varlet). of l a b o r a t o r y animals ( i i , 1 2 , 1 3 ) a in the n (18). c l a r i f y the ~ sslble i olve nt of PG in o u r exper[ ntal t e r m l n a t l o n of p ancy b y i ocln or c o r t l s o , a c o n s l s t e n t I n h i o i t o r of PG s y n ~~hesls a /or releas~ )j wa $ sc euled c o n c u r r e n t l y w i t h ~ . It was, however, obse ed that a slmulta ous a d m i n i s t r a t i o n of e l t h e r i ocln or c o r t i s o c o n c u r r e n t l y with SG c o n s l s t e n t l ) rsed t a i f e r t l l l t y effe of P G. T~ g~ h s t a t u s of fetu s, p l a ce ae a c pora lutea was found identical to t h a t co ed in t controls (Table). T h e fetal su IvaI rate as c a l c u l a t e d on d a y 16 of egnancy %n i oci a cortiso -t a d animals w a s 9 3 . 6 a .~/, s ct e l % as against t co rol 1 o~ . (Table). m t h i s c o l l e c t i v e data I t could assu d t t the lu al demise a fetal r e s o r p t i o n as e v i d e n t following ~ ~ 91 n are s s i b l y the c o n s e q u e n c e s o f an excessive a v a i l a o l l i t y o f PG. I t has been recorded t h a t the p gnant r a t u t e r u s has an a b l l l t y t o s y n t ~ s l z e a release 2a when t blo t l t e r of e s t r o g e n is high (I0). nversely, a cot~siderable a u of a c c u m u l a t i o n at the f o l l i c u l a r and luteal level is e v i d e n t in hu n, rat and so o t h e r species of animals {20~21). R e c e n t fl ings from our l a b o r a t o r y also pro se that estrogen mig cause l u t e o l y s l s by s t i m u l a t i n g at the o v a r i a n level (22).. T refore, to rlfy t ~ p o s s i b i l i t y of action b y stimulat| ~ at t u fine o~ arian I i, bila rally hyste c%omlzed cycli rats re made pse o egnant by sterile m a t i n g a ~ subjec to t gl n. It was, vet, r e co ed that I0 IU of P on d a y 5 of ~ e u c o e g n a n c y cons is tently te Inated t state of p o g n a n c y by day I0-12. T c o r p o r a ]u a of t se anl Is re~ fou to be s m a l l e r as c a d to c o n t r o l s o n d a y 14 of pse op gnancy (3.1 _+ 0.I vs 2.0 +_ 0. I ). ersely, w h e n ;~ndocin was s c h e d u l e d to the bila rally h y s t e r e c t ~ n l z e d p s e u d o p r e g n a n t animals along w i t h the , no a! d u r a t i o n of pseuoo egnancy (18-20 days) was rained. O u r e x p e r i m e n t a l findl s, therefore, ag e with ~enbach e~ al. (23) t h a t the l u t e o l y t l c Interaction tween F ~ and e s t r a d l o l o c c u r s at t o v a r i a n level a ~ is i n d e p e n dent of the uterus.

ACKi~ The e n c o u r a g i n g c o o p a t l o n of Dr. T ....M.a h o n e y , ...Dr. .. 3, S p i e l e r a ~ ...Dr, .

~

~ Z, A l o k ,

G0pta,

9o h a d o t r o p h t n Proge ttli fficac7 of ( ~ h ........3 t 506, 1 9 7 6 .

S 50

n a~ te

tterj o~

~S

S a b i t a T e j u j a , Dr. ..S, .. 3. Segal, Dr. B a r t k e .....is . ..... fully ack wledged.

kE ~ 1,

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S ee

,Amar =.... ~ e g n a

o r .. p r o 1 a c t i n .. S e r u m

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J UN El 978

serum

..

nt t fe r-

V O L. 17 N O' 6

CONT

21 t

CE

I

Chattezjae,Amar, ~ l , A l o k K. a ~ Gupta,Tarun z |)regnant mare's serum 9onadotrophin. I [. ReversaI o f the a n t l £ezti I i t y f a c u i t y of pregnast mare's serum 9onadot ph~n by using clomiphene c t r a t e oz ~o~se~pine r at s. ~ st race pt i on 15 = 1, 1977.. ....

.....

Chatterjee,Amar, ~ l , A l o k K. a ~ Gupta Ta~un : ~egnant mare's serum 9onadotrop~.n. [ [ [ I ~ m i s p a y [ ~ and the ve~sai of the a n t i f e r t £ 1 t y f a c u l t y o£ p gnant 's serum gonadotropin. Fert I . I . 28 : I i01, i

Armstrong, T. and G ep, .0. : F a l l e of d e c l d u a l res nse to uterine trauma~ e f f e c t s of U~ ( ~ t e i n [ z i n g r m o s e ) on e s t r o g e n secretion in rat s w% ovar le s lute in ized by e x o g e n o u s go nadotzop% ns. E n d o c r %nO I ~ y 76 : 246, 1965 . . . . . . . .

Q

Se n, K-, Pa I, k.K. Chat te rj ee ,A. i E s troge s and .f....ema le fe r t I I ity l. F a i l u r e of human chozi nic 9 o s ~ o t r o p n or 2es o~rpine in the zeversal of pre 9sa ncy was t age b y e st io i ¢ ~ope ntv ipro i onate. ~ n t race pt [on 16 z II, 1977.

~

ok~B., luteolysis i 974.

in ewe:

, possibie

L. and si~e of action.

...V. . I Estrogen i~uced £ndocrlnology 9~ z ii97

..

....

5tormshak,F., lley, i.E and H a w k , . . f u n c t i o n by e s t r a d l o ! ~ 1 7 B . J.Anim.Sc. I

:

O

P9 : 476,

on of ov ne luteal 1969.

Karsch~F.J O , e y , L C. ick,B ...F.• Di~rschk~,D.J O a tlonal iuteolysls in the Rhesus moskey. Endoclinology

St

.

10.

~ob 92

I, . = FuncI143, 1973.

Go re,B.Z., Caidwell,B.V. and . ~p.ro~ ... f{,L. : £ s t r o . .n-in6uce~ . . . . . .human . . . .luteo .... IyS%S. J . C l i n . E ~ o c I ~ ,J~ t a b • 36 : 615, 197S Aikes,J~W. ~ A s p i r i s ~no i ~ o m e t h a c i n pro osg r t u r i t i o n in z ts : e v i d e n c e that p r o s t a g l a ins c o s t z l b u t e to e x p u l s L o n o~ fetus, i~ature ( ~ n d . ) ....240 : 21, 1972. . . . . . . ....

Chatterjee,A

..: .. The possible mode of a. c~[on ~ of p r o s t a g I a ~ [ n s XI[. D i f f e r e s t l a l e f f e c t of pro s t a g l a n d l n F~a ~n ! ~ u c [ n g premature evacua .... tion of conceptus in the ~ntact and c strated p r e q n a n t rat. P r o s t a q l a n dins 12 : I(M55, ~976. ..... ....

II

Horton, ~:.W.& ~ r l e y , P . B . = An invest~qatlon of t poss[bie e f f e c t s of pro ns a ~ F2a on Pregnancy in mice a ~ r a b b i t s . Brlt.J. Pha~macol. 36 , i8~, 1969. .... .~bhset~ar,A.P. = E f f e c t s cesses of hamster~ and rats.

I

4. 15.

pzostaglanc In F2a on so repr J. 5~ : ' 1972.

Vane,J.R.° : Inhib%tion of p r o s t a g l a n d i n synthesis ~ a t U r e New Biol. 2~I tion for ike dru~s.

Rothch~l ; I . ....: The cot e(~ ec t of 107, i965.

i U N E 197 8 ...V OL. 17 N O. 6

u c t i v e p~o-

s a m e c h a n i s m of ac: 23~ 1971.

s luteum-hyp~phys~s r e l a Ion : s h i p . The l u t e o ! y t i c . A.cua ~ e ~ o c r . ( ~ h . %. .... : (~)in t ~ rat .... ......

~~~

$51

6

FIInt,A.P.F., Ande~son,A.B.M., ~ t n,P.T, a ~rnbuil,A.C. = ntrol utoIoarian venous prostagla in F during l a ~ u r in sheeptacute effects of vaginal and ¢ervlcal stimulation. J . E ~ o c r l n o l . 6.g= , 1974. of

17.

8

~bhse ar,A.P, and tson,D, t mpo;al relationship ~ pattexns of gonadotrophlns, oes osen, pro stlns a ~ ~ F rient rats. Biol.Reprod. I0 = I , 1974 ~zim,S.M.M. F2a. ~ncet

a

Filshie,O.M. I t 157, 1970.

t Therapeutic

a

ion u s i ~

en secreto in ~ e p a r t u prostagla~in

zak,J. = Suppression of the by hyd~rocoztisone ~ .

19.

rbaczynskadzo,K, a Staszewska-~ re idase o£ prostagla in-like subs£ances Prostagla ins 13 = 517, I 7.

20.

He~erson,K.M. a Natty,K.P. : A bioc c a l h y ~ t h e s l s to e x p l a i n the chanism of luteal reg ssion, os~ ~Ji~a ins 9 = 7 ~ , 1975.

21.

De zs,L.M., Be man,H.R, a eep, R.O. t ~ffects of p staglandins and gonadotxophln on luteal p z o s t a g l a ~ I n a steroid biosynthesis. Advances in B1osci. 9 = 701, 1973.

224

C h a t ~ r J e e , A . , Sen,K. a Basu,R. = Estrogen a female fertillt7. II. [ ~ o thacin and t versal of the luteolytic efficacy of estrodlol cyclo ntylpropionate, ntraceptlon 17: 163, 1978.

23.

~ e n b a c h , ~ . R . , Hixon,J.E. a bet en estradio] a ~ostagla Repr . 16 = 571, 1977.

nsel,W. = A luteolytlc interaction in F2a in hysterectomized ~ e s . Biol.

J U N E 1 9 7 8 ~V O L . ! 7 N O 6