Endocrinology, Vol 127, 2726-2737, Copyright © 1990 by Endocrine Society

ARTICLES

Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

C Martel, C Labrie, E Dupont, J Couet, C Trudel, E Rheaume, J Simard, V Luu-The, G Pelletier and F Labrie
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada.

The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) [10 IU, twice a day (bid)], ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered, singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells. The present data show that hCG and PRL exert potent and opposite cell- specific effects on ovarian 3 beta-HSD expression, activity, and content in the rat ovary. Moreover, the present study could suggest that female infertility associated with hyperprolactinemia in women could well be related, at least in part, to the potent inhibitory effect of PRL on ovarian 3 beta-HSD expression and activity.

This article has been cited by other articles:

				M. Hamel, I. Dufort, C. Robert, C. Gravel, M.-C. Leveille, A. Leader, and M.-A. Sirard Identification of differentially expressed markers in human follicular cells associated with competent oocytes Hum. Reprod., May 1, 2008; 23(5): 1118 - 1127. [Abstract] [Full Text] [PDF]

				C. Stocco, C. Telleria, and G. Gibori The Molecular Control of Corpus Luteum Formation, Function, and Regression Endocr. Rev., February 1, 2007; 28(1): 117 - 149. [Abstract] [Full Text] [PDF]

				J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family Endocr. Rev., June 1, 2005; 26(4): 525 - 582. [Abstract] [Full Text] [PDF]

				J. M. Bowen and P. L. Keyes Repeated Exposure to Prolactin Is Required to Induce Luteal Regression in the Hypophysectomized Rat Biol Reprod, April 1, 2000; 63(4): 1179 - 1184. [Abstract] [Full Text]

				J. M. Bowen and P. L. Keyes The Proestrous Prolactin Surge Is Not the Sole Initiator of Regressive Changes in Corpora Lutea of Normally Cycling Rats Biol Reprod, November 1, 1999; 61(5): 1208 - 1215. [Abstract] [Full Text]

				F. A. Feltus, B. Groner, and M. H. Melner Stat5-Mediated Regulation of the Human Type II 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene: Activation by Prolactin Mol. Endocrinol., July 1, 1999; 13(7): 1084 - 1093. [Abstract] [Full Text]

				C. Bole-Feysot, V. Goffin, M. Edery, N. Binart, and P. A. Kelly Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice Endocr. Rev., June 1, 1998; 19(3): 225 - 268. [Abstract] [Full Text]