ROLE OF 5-ALPHA-REDUCTION IN PROGESTERONES ABILITY TO RELEASE FSH IN ESTROGEN-PRIMED OVARIECTOMIZED RATS

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, NN-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 [H-3]progesterone. Substrate, ([H-3]progesterone) and product ([H-3]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.