INVITRO EFFECTS OF DIHYDROTESTOSTERONE ON GRANULOSA-CELL PRODUCTION OF ESTROGEN AND PROGESTERONE

To investigate the direct effects of androgens on follicle development, intact, immature female rats were given 8 IU PMSG (0 hour) and four injections of either vehicle or dihydrotestosterone (DHT), 1 mg/kg body weight, at 0, 12, 24, and 36 hours after PMSG. Granulosa cells from small (< 200-mu-m), medium (200 to 400-mu-m), and large (> 400-mu-m) follicles were isolated and cultured in the presence or absence of 0.5-mu-M DHT in vitro for 48 hours, and the medium was assayed for progesterone and estrogen. Results show that DHT caused an increase in progesterone accumulation in all granulosa cells, regardless of follicle size. However, DHT inhibited estrogen accumulation in granulosa cells from different-size follicles and the inhibition varied depending on the duration of androgen exposure in vivo. The inhibition of estrogen accumulation was seen in granulosa cells from small follicles without prior exposure to DHT in vivo, while an inhibition of estrogen accumulation was seen in granulosa cells from medium and large follicles exposed to DHT treatment in vivo. Taken together, the results of experiments with in vivo and/or in vitro DHT treatment show that the androgen increases granulosa cell progesterone synthesis regardless of follicle size. However, the estrogen accumulation by granulosa cell is dependent on follicle size and duration of DHT exposure.