Effect of the antiprogesterone RU-38486 on the steroids levels throughout the rat estrous cycle

-117 STEROIDOGENESIS IN EARLY FETAL BOVINE GONADS* Dominguez M.M., Liptrap R.M. and Basrur P.K., Department of Biomedical Sciences, University of Guelph, Guelph, Ontario NlG 2W1, Canada Gonadal steroid synthesis and secretion patterns were examined in 24 bovine fetuses of 45 to 110 days of gestation, to determine the physiological correlates of gOn8d81 morphogenesis in cattle. Hormonal synthesis was studied by histochemical tests for 38- and 17g-hydro~6teroid In vivo and -in vitro secretion patterns of testosterone, androdehydrogenaae (HSD) enzymes. -stenedione, estradiol and estrone were determined in amniotic and allantoic fluids and in media from 24 hour gonadal cultures. All 4 steroid levels in allantoic fluid of female fetus66 and all but testosterone in allantoic fluid of males showed a positive correlation (r=>.7) with age while in the amniotic fluid, only androstenedione in males and all but teetosterone in females were positively correlated with age. Male fetuses had significantly higher mean testosterone levels (PeO.05) in both amniotic and allantoic fluids and higher androetenedione levels in amniotic fluid. The reaction for 3S-HSD was positive in testes of all ages (n=8) and negative in all ovaries (n-16) except those from 4 fetuses of 45 to 65 days. The reaction for 1?6-HSp was negative in all gonads except 2 ovaries of 45 to 65 day fetuses. Testosterone secretion In vitro testicular remained consistently high in male fetuses of all ages examined. The -steroid secretion rate from 45 to 75 days was higher (P
the experiment the rats were killed and the adrena? weights recorded. Rats injected with RU displayed different degrees of vaginal cornification on the day of diestrus-2: O/11, 5/8, found during diestrous.

6/9, and 819 respectively. No significant differences in E2 levels were On the contrary RIJ-5 treated rats seem to have a prolonged P secretion. At autopsy (diestrus-1 of the next cycle) RU-5 treated rats had an increased adrenal weight. RU 38486 has an antl-P effect (vaginal cornification).The prolongation of P secretion detected in RU-5 treated rats may be the reflection of either a blockage of the inhibitory effect of P on LH secretion during diestrous resulting in a rise of LH which probably stimulates P secretion or, a blockage of a possible negative feed-back of P on its own secretion, Due to the antig~UCOCOrtiCOid effect of RU (increased adrenal weight), adrenal P may be contributing to the higher serum levels of P found during diestrus-2, The authors thank Dr. Niswender and Dr. Collins for the gift of antiprogesterone (GON-337) and antiestradiol 17p (E T&K) serums, We are grateful to Roussel-Uclaf Labs. for their gift of RU-38486. This work hai been made possible throuqht a qrant from FISS (Spain). -119 HUi+%N PLctCfNTAt SUtPtJrriTASE ACTIVlTY /AtJO BEPRESSED BY HYP~RPRO~CTINA~~II~~ ; Egged Post graduate Med. School, 1389 Budapest;

ESTROGEN 3.: Dept. HUiJGARY

SYNTHESIS/ of Obstet

COULD DE and Gynecol.,

Human placental microsomes \vere prepored on the basis of Gibb's method 1984/ end some technical modifications /Gibb et al.. Endocrinol., 114, 2323, 106, 295, 1985/. The placental r~ere published in J.Endocrinol. /Egyed et al., steroid aulphatase activity for dehydroepiandrosterone-3@-yl eulphate /JHASO .'//DHn conversion /l./ and apparent Michaelis constants /t<,/ for "-/DHA /2,/ were measured in vitro in the presence of diffeben: concentr tzona of hProlactin in the experimental bathes /50 or 250 ng/ml/. BHASC4 RESULTS: /l.,I The average of DHASO -/DHA hydrolysis in 50 ng/ml hPRLmilieu VJ~S higher than in 250 ng/ml hPRe-milieu /33.67> 29.88 pm01 @I-IA/So min x act.protein; 6 placentas; corr.coeff. =o.996, in pared T test T = 5.25: significant/. pco.01; placental steroid sulphatase was /2./ The apparent I< of human significantly lower /which is nor~alf in 50 ng/ml hPRL-milieu rhan 250 ng/ml = 25.4q69.65 * corr.coeff. 0,997 and o.999/. jKM Summarizing o;r data we could suppose that hvperpiolactinaemie /in late pregnancies or in casee of prolactinomas in pregnancies/ could deprees the as a rate-limiting feed back for the placental placental estrogen synthesis: steroid sulphatase activity.

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