RECOMBINANT HUMAN INHIBIN-A ADMINISTERED EARLY IN THE MENSTRUAL-CYCLEALTERS CONCURRENT PITUITARY AND FOLLICULAR, PLUS SUBSEQUENT LUTEAL, FUNCTION IN RHESUS-MONKEYS

Inhibin, a suppressor of pituitary FSH secretion in nonprimate species , may also act in the ovary to regulate follicular development. To exa mine whether inhibin has similar actions in primates, female rhesus mo nkeys (n = 3/treatment), exhibiting regular menstrual cycles, received sc injections of either vehicle or 60 mu g/kg recombinant human inhib in-h at 0800 and 1600 h for 5 days beginning at menses. The vehicle-tr eated monkeys displayed menstrual cycles of normal length, with the fo llicular (11.3 +/- 2.5 days, mean +/- SE) and luteal (16.3 +/- 2.5 day s) phases demarcated by midcycle peaks in serum estradiol(E) and bioac tive LH. After the first inhibin injection, levels of immunoreactive i nhibin A peaked at 10 ng/mL within 1 h and returned to baseline (<0.1 ng/mL) before the second injection 8 h later. Although serum E and LH did not change, bioactive FSH decreased (to 66% of pretreatment levels , P < 0.05) within 8 h. Within 1 day, circulating bioactive FSH was le ss (P < 0.05) in inhibin-treated monkeys, compared with controls. By 2 -3 days, serum E levels were also markedly (P < 0.05) reduced in inhib in-treated animals, whereas bioactive LH rose 3-fold (P < 0.05). After inhibin treatment, the midcycle rises in serum E and LH were delayed; hence, the follicular phase was prolonged (15.0 +/- 2.6 days, P < 0.0 5), compared with controls. Although the patterns and levels of serum LH circulating during the subsequent luteal phase seemed comparable in both groups, mean progesterone levels were suppressed to 2-3 ng/mL (P < 0.05) during the midluteal phase in inhibin-treated monkeys. Howeve r, the length of the luteal phase in inhibin-treated cycles (13.0 +/- 2.6 days) was not significantly altered. We conclude that exogenous in hibin rapidly diminishes pituitary FSH secretion in female monkeys dur ing the early follicular phase of the menstrual cycle. This action, an d/or other actions directly on the ovary, leads to subsequent effects on follicular steroidogenesis and pituitary LH secretion that culminat e in an aberrant ovarian cycle characterized by an insufficient luteal phase. The study identifies, for the first time, possible activities and roles of inhibin during the ovarian cycle in primates.