MODULATION OF PROGESTERONE SECRETION BY ANDROGENS IN PORCINE GRANULOSA-CELL CULTURES

The influence of testosterone, androstenedione and dihydrotestosterone (DHT) on the progesterone (P4) production by cultured porcine granulosa cells was studied in the presence or absence of gonadotropins. Porcine granulosa cells from large follicles (6-12 mm in diameter) were incubated for 2 days with 5% CO2 in air with testosterone, androstenedione and DHT (10(-12), 10(-10), 10(-8) and 10(-6) M) in the presence or absence of luteinizing hormone (LH, 10 ng/ml) or follicle-stimulating hormone (FSH, 30 ng/ml). P4 and pregnenolone (P5) in conditioned culture media were quantified by their specific RIAs. In the absence of gonadotropins, P4 in media with androgens were not significantly different from controls. In the presence of LH, the addition of testosterone (10(-10), 10(-8) M), androstenedione (10(-8) M) and DHT (10(-8) M) caused a significant 1.3- to 2.3-fold increase in P4 over that caused by LH alone. In contrast, in the presence of FSH, testosterone (10(-12), 10(-10) M), androstenedione (10(-12)-10(-6) M) and DHT (10(-6) M) reduced the levels of P4 by 22% to 41%. The addition of androgens with LH caused a significant increase in P5, while P5 decreased in the presence of FSH. P4/P5 ratios remained unchanged in the presence of both LH and FSH. These data suggest that the P4 production by cultured porcine granulosa cells is modulated in a paracrine or an autocrine fashion by androgens in the presence of gonadotropins, and that androgens may exert their actions partly by altering the activity of cholesterol side chain cleavage enzymes.