ANDROGENS AUGMENT VASOACTIVE INTESTINAL PEPTIDE-RELEASING AND GROWTH HORMONE-RELEASING HORMONE-STIMULATED PROGESTIN PRODUCTION BY RAT GRANULOSA-CELLS

Vasoactive intestinal peptide (VIP) has been shown to stimulate steroid production by cultured rat granulosa cells independently of FSH. In the present study, we have examined the modulatory effects of various steroids on this response. Rat granulosa cells cultured for 2 days with only VIP showed small but significant increases in progesterone and 20alpha-dihydroprogesterone (20alpha-OH-P) production. Concomitant treatment with either a synthetic estrogen (diethylstilbestrol), a synthetic progestin (R5020), or cortisol did not augment VIP-stimulated progesterone production; however, the latter two steroids slightly, but significantly, augmented VIP-stimulated 20alpha-OH-P production. In contrast, concomitant treatment with a synthetic androgen (R1881) dramatically augmented both VIP-stimulated progesterone and 20alpha-OH-P production. These effects were dose dependent for both VIP and R1881 and could be blocked by the androgen antagonist cyproterone acetate. Time course studies revealed that progesterone content of the culture media rapidly increased over the first 24 h of culture then remained fairly constant for the next 48 h; 20alpha-OH-P content, on the other hand, was low for the first 12 h of culture and steadily increased thereafter. Dose-response analysis for R1881 revealed an ED50 of approximately 2 x 10(-8) m for the synthetic androgen, and comparison with other naturally occurring androgens provided the rank order of potency R1881 > androstenedione > testosterone = dihydrotestosterone. Additional studies with another member of the VIP peptide family, GH-releasing hormone, showed dose-dependent stimulation of progesterone and 20alpha-OH-P production by this peptide. These effects were also augmented by R1881 but not by diethylstilbestrol, R5020, or cortisol. These studies demonstrate that androgens, but not estrogens, progestins, or glucocorticoids, augment VIP- and GH-releasing hormone-stimulated progestin production by cultured rat granulosa cells.