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5-
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*



Medical Research Council Group in Molecular Endocrinology, CHUL Research Center and Laval University Quebec, G1V 4G2, Canada
Address correspondence and requests for reprints to: Professor Fernand Labrie, Laboratory of Molecular Endocrinology, CHUL Research Center, 2705 Laurier Blvd., Quebec GlV 4G2, Canada. Tel.: (418) 654-2704. Fax: (418) 654-2735.
Abstract
The enzyme 3β-hydroxysteroid dehydrogenase/
5-
4 isomerase (3β-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3β-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3β-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 3β-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) [10 IU, twice a day (bid)], ovine FSH (0.5 µg, 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 3β-HSD mRNA content accompanied by a similar decrease in 3β-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 30- 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 3β-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 30-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3β-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3/8-HSD mRNA accumulation in interstitial cells. The present data show that hCG and PRL exert potent and opposite cell-specific effects on ovarian 3j8-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 3β-HSD expression and activity. (Endocrinology 127: 2726–2737,1990)
Footnotes
* This work was supported by grants from the Medical Research Council of Canada (MRC Group in Molecular Endocrinology), Le Fonds de la Recherche en Sante du Quebec (FRSQ), and Le Fonds pour la Formation de Chercheurs et l'Aide a la Recherche (to F. L., G. P., J. S. and V. L.-T.).
C. M., C. L., J. C, and C. T. are supported by Fellowships from the FRSQ.
Received July 2, 1990.
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