Estrogens, progestogens, and androgens enhance the follicle-stimulating hormone-stimulated plasminogen activator production by cultured rat granulosa cells

We have previously shown that FSH caused a dose-dependent increase in plasminogen activator (PA) production by cultured rat granulosa cells. PA production was assayed by culturing granulosa cells, obtained from immature diethylstilbestrol-treated rats, on [125I]fibrin plates and determining the extent of fibrinolysis after the addition of the specific substrate plasminogen. To study the effect of ovarian steroids on FSH-stimulated PA production, concomitant treatment with FSH and estradiol [(E2) 10(-7) M], progesterone [(P) 10(-6) M], testosterone [(T) 10(-7) M] or 5 alpha-dihydrotestosterone [(DHT) 10(-7) M] were tested in these cultures. Treatment with E2 significantly enhanced the FSH-stimulated PA production by 35-210% over the whole range of the FSH dose response curve. The augmentation of FSH-stimulated PA production by E2 was not affected by the concomitant treatment with the antiprogestin RU 486 (10(-6) M). Similarly, P significantly enhanced the FSH-stimulated PA production by 34 to 90%. The stimulating action of P on FSH-dependent PA production was blocked by the simultaneous treatment with RU 486. Concomitant treatment with T significantly increased the FSH-induced PA production by 22-60%. That the effect of T was not due to the aromatization to E2 was evidenced by the augmentation by DHT of FSH-stimulated PA production. DHT caused a significant 20-39% enhancement in the responsiveness of the granulosa cells to FSH by further increasing PA production. The enhancement of PA production by androgen is decreased partially by concomitant treatment with the antiandrogen flutamide (10(-5) M) and the antiprogestin RU 486. These in vitro data demonstrated the importance of estrogens, progestogens, and androgens in modulating the stimulating effect of FSH on PA production by immature rat granulosa cells.