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Direct stimulation of ovarian progesterone-metabolizing enzyme by gonadotropin-releasing hormone in cultured granulosa cells.

Authors: Jones, PB  Hsueh, AJ 
Citation: Jones PB and Hsueh AJ, J Biol Chem. 1981 Feb 10;256(3):1248-54.
Pubmed: (View Article at PubMed) PMID:6778878

The mechanism by which gonadotropin-releasing hormone (GnRH) inhibits ovarian progesterone production was investigated by studying the GnRH modulation of 20 alpha-hydroxysteroid dehydrogenase activity in cultured rat granulosa cells. The granulosa cells obtained from hypophysectomized, estrogen-treated rats were treated with various hormones in vitro and 20 alpha-hydroxysteroid dehydrogenase activity determined by measuring the conversion of radiolabeled 20 alpha-hydroxy-pregn-4-en-3-one to progesterone. Treatment with follicle-stimulating hormone (FSH) increased the 20 alpha-hydroxysteroid dehydrogenase activity of granulosa cells to 1.3-fold of the control value. Concomitant treatment with 10(-8) M GnRH further enhanced the FSH stimulation of enzyme activity to 2.6-fold of the control value. The increases in 20 alpha-hydroxysteroid dehydrogenase activity were associated with increases in maximum velocity, while the Km values remained unchanged. In contrast, prolactin (PRL) treatment of FSH-primed granulosa cells resulted in an 88% decrease in 20 alpha-hydroxysteroid dehydrogenase activity as compared to untreated controls. Concomitant treatment with GnRH partially blocked this inhibitory effect. Furthermore, incubation of granulosa cells for 2 days with GnRH alone resulted in a 2.7-fold increase in 20 alpha-hydroxysteroid dehydrogenase activity, as compared to untreated controls. In all experiments, the effect of GnRH was blocked by concomitant treatment with a GnRH antagonist. These results suggest that one mechanism by which GnRH inhibits FSH- and PRL-stimulated progesterone production in granulosa cells is through the stimulation of the activity of 20 alpha-hydroxysteroid dehydrogenase which converts progesterone to a less active metabolite.

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CRRD Object Information
CRRD ID: 10053621
Created: 2015-07-16
Species: All species
Last Modified: 2015-07-16
Status: ACTIVE



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