Evidence for a granulosa cell site of dihydrotestosterone metabolism in the adult rat ovary

Abstract

The ovarian enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD) converts dihydrotestosterone (DHT) to 5a-androstan-3a,17b-diol (3α-diol), a reduced androgen that does not bind to the granulosa cell androgen receptor. To determine the relative contribution of the granulosa cells to total ovarian 3α-HSD activity, adult rats treated with either medroxyprogesterone acetate (MPA) or vehicle underwent ovarian microdissection. 3α-Hydroxysteroid dehydrogenase is primarily located in excised follicles and corpora lutea, and is inhibited in the follicles but not corpora lutea by MPA (P<0.05). Elimination of healthy granulosa cells while maintaining healthy theca cells by irradiation of the exteriorized ovaries with 6000 rads resulted in a marked reduction in 3α-HSD to 19% of control levels on a pre-organ basis (P<0.01). The granulosa cell is the major ovarian site for 3α-hydroxylation of ring A-reduced C19 steroids in the adult rat.