title: Role of 5 alpha-reduction in progesterone's ability to release FSH in estrogen-primed ovariectomized rats.
abstract: In ovariectomized estrogen-primed rats, progesterone as well as 5 alpha-dihydroprogesterone (5 alpha-DHP) are capable of inducing the release of gonadotropins. This study examined the need of 5 alpha-reduction as a prerequisite for the action of progesterone. The 5 alpha-reductase inhibitor, N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide was injected at a 1 or 2 mg dose/rat 2 h prior to an injection of 0.4 or 0.8 mg progesterone/kg body weight at 0900 h to immature ovariectomized, estrogen-primed rats and serum was analyzed for LH and FSH at 1500 h. Pituitary and hypothalamic 5 alpha-reductase activity was measured at the time of progesterone administration and at the time of the surge by incubating tissue homogenates with [3H]progesterone. Substrate, ([3H]progesterone) and product ([3H]5 alpha-DHP), were separated by reverse phase HPLC. The pituitary 5 alpha-reductase activity was not blocked at 1500 h. However, both pituitary and hypothalamic 5 alpha-reductase was blocked at the time of progesterone administration. No effect was seen by acute administration of the 5 alpha-reductase inhibitor upon either the 0.4 or 0.8 mg progesterone/kg-induced release of LH and FSH. There was, however, a specific, significant inhibition of progesterone-induced FSH but not LH release when the 5 alpha-reductase inhibition was sustained throughout the afternoon of the gonadotropin surge. These results indicate a biologically significant role for the irreversible 5 alpha-reduction of progesterone in the modulation of the release of FSH.
authors.affiliation: Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000.
authors.forename: C
authors.initials: C
authors.lastname: Putnam-Roberts
authors.forename: D W
authors.initials: DW
authors.lastname: Brann
authors.forename: V B
authors.initials: VB
authors.lastname: Mahesh
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D010052:Ovariectomy; D010084:Oxidation-Reduction; D010902:Pituitary Gland / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011375:Progesterone Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D013047:Specific Pathogen-Free Organisms; D013379:Substrate Specificity
chemical_list: D000726:Androgen Antagonists; D001378:Azasteroids; D004967:Estrogens; D013196:Dihydrotestosterone; D011374:Progesterone; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D011375:Progesterone Reductase