Ovarian regulation of hypothalamic and pituitary progestin-metabolizing enzyme activities

Progesterone 5 alpha-reductase activity and 5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) activities (NADH-linked) were measured in hypothalamic and pituitary tissues from rats during various stages of the estrous cycle and in ovariectomized rats treated with 17 beta-estradiol or vehicle. Enzyme assays were performed using 3H-labeled steroid substrates and reverse isotopic dilution analyses. Pituitary 5 alpha-reductase activity fluctuated over the estrous cycle, with peak levels observed on proestrus, estrus, and metestrus and lowest levels on diestrous 1 and 2 of 5-day cycling rats. Pituitary NADH-linked 3 alpha-HSOR activity also fluctuated over the estrous cycle, paralleling 5 alpha-reductase activity. The pituitary NADPH-linked 3 alpha-HSOR activity and three hypothalamic enzyme activities, the 5 alpha-reductase, NADH-linked, and NADPH-linked 3 alpha-HSOR activities, did not change over the estrous cycle. After ovariectomy (10 days), pituitary 5 alpha-reductase activity was elevated 10- to 12-fold relative to mean levels in intact rats, while the pituitary NADH-linked 3 alpha-HSOR activity was elevated 4- to 5-fold. Treatment for 3 days with estradiol benzoate (10 micrograms/day) significantly reduced both pituitary 5 alpha-reductase and NADH-linked 3 alpha-HSOR activities to about half the levels observed in ovariectomized rats. The pituitary NADPH-linked 3 alpha-HSOR activity was unaffected by ovariectomy. After ovariectomy, a small decrease was observed in the hypothalamic 5 alpha-reductase; no differences were observed in the NADH-linked or NADPH-linked 3 alpha-HSOR activities of the hypothalamus compared to mean levels in cyclic rats. The results suggest a role of the ovary in the regulation of the pituitary and hypothalamic progesterone 5 alpha-reductase and pituitary NADH-linked 5 alpha-dihydroprogesterone 3 alpha-HSOR activities.