TESTOSTERONE PROCESSING BY PITUITARY-CELLS IN CULTURE - AN EXAMINATION OF THE ROLE OF 5-ALPHA-REDUCTION IN ANDROGEN ACTION ON THE GONADOTROPH

Dispersed rat pituitary cells were exposed to [1,2,6,7-H-3]testosterone ([H-3]T, 10(-8)M) to assess the role of 5-alpha-reduction in T regulation of gonadotroph secretion. After 4 to 48 hours of exposure, [H-3]T metabolites isolated by thin-layer chromatography were characterized in medium and cell homogenates as well as bound to androgen receptors salt-extracted from purified nuclear pellets. Receptor-bound 5-alpha-[H-3]dihydrotestosterone ([H-3]DHT)/total [H-3]androgens rose progressively from 16% at 4 hours to more than 50% at 48 hours. Coincubation with 4-MA (10- to 1,000-fold molar excess) or testosterone-17-beta-carboxylic acid (TCA: 1,000-fold excess) reduced receptor-bound [H-3]DHT/[H-3]androgen to less than 10% and 20%, respectively, but elevated [H-3]T-receptor levels. Despite inhibiting 5-alpha-reductase activity, TCA and 4-MA had no effect on T suppression of gonadotropin-releasing hormone-stimulated luteinizing hormone secretion or T enhancement of total (cell + secreted) follicle-stimulating hormone levels. The results suggest that 5-alpha-reduction to DHT is not essential for the expression of the direct influences of T on gonadotropin synthesis and secretion in rat gonadotrophs.