Progesterone inhibits basal production of follicle-stimulating hormone in ovine pituitary cell culture

Progesterone (P₄) regulation of FSH production was studied in dispersed ovine pituitary cell culture. FSH secretion into culture media was decreased by 30–70% in the presence of 10^-7 m P₄. The ED₅₀ of P₄ was 2 × 10^-10 m. Decreased FSH secretion was observed as early as 9–12 h after treatment with P₄ (10^-7 m). FSH secretion rebounded to control levels after P₄ was removed for 4 days. The intracellular FSH content also decreased after P₄ treatment, suggesting that decreased FSH secretion is due to decreased biosynthesis. Two progesterone metabolites, 5α-dihydroprogesterone and 17α-hydroxyprogesterone, showed relative activities of 39% and 28%, respectively, compared to P₄. Although testosterone (10^-7 m) inhibited FSH secretion by 10%, it may have done so only via conversion to estradiol. Dihydrotestosterone, androstanedione, and cortisol had no effect on FSH secretion. P₄ consistently showed activity in 2-day-old ovine culture, but its effect essentially disappeared by day 10 or 12 of culture. When insulin was included in the culture medium (medium 199 plus 10% charcoal-treated anestrous ewe serum), the effect of P₄ was maintained for up to 20 days, and FSH production, in general, was augmented with insulin. These results indicate that P₄ can specifically inhibit FSH production in ovine pituitary cell culture, but there is no long term maintenance of the P₄ response unless insulin is present. Finally, it is known that 17β-estradiol also inhibits FSH production in ovine pituitary cultures. Therefore, our results establish that FSH production is a phenomenon that is regulated similarly by both estradiol and P₄.