SYSTEMIC AND INTRALUTEAL INFUSION OF INHIBIN-A OR ACTIVIN-A IN RHESUS-MONKEYS DURING THE LUTEAL-PHASE OF THE MENSTRUAL-CYCLE

The endocrine or local actions of inhibin-related peptides synthesized by the primate corpus luteum (CL) remain undefined. This in vivo study was designed to determine whether exogenous inhibin or activin modulates pituitary gonadotropin secretion and the functional life span of the CL during the luteal phase of the menstrual cycle. Beginning at midluteal phase of the cycle, either vehicle or 1 mug/h of recombinant human inhibin A or activin A (n = 3-6 per treatment group) was infused into rhesus monkeys via the jugular vein (i.e., peripheral infusion) or directly into the CL (i.e., intraluteal infusion) by means of an osmotic minipump for 7-14 days. Daily samples of saphenous venous serum were assayed for estradiol (E) and progesterone (P) content by RIA, and for FSH and LH levels by bioassay. Intraluteal infusion of inhibin or activin did not alter circulating P levels or the length of the luteal phase compared to those values in vehicle-infused controls. Likewise, LH levels were not different between the three groups. However, FSH levels declined progressively during inhibin infusion to 26% of pretreatment levels (p < 0.05), whereas FSH levels in vehicle-infused controls were unchanged for several days and then rose (p < 0.05) to peak levels around menses. FSH levels did not change significantly during activin infusion into the CL. Although similar results were obtained in monkeys receiving peripheral or intraluteal infusions of inhibin, events following the peripheral infusion of activin were markedly different from those during intraluteal administration. Peripheral activin treatment caused a sustained reduction in serum LH and P levels (p < 0.05) and shortened the length of the luteal phase compared to that in control cycles (9.2 +/- 0.3 vs. 14.7 +/- 1.3 days, p < 0.05). The data provide the first evidence that exogenous inhibin selectively suppresses FSH levels in primates during the mid-to-late luteal phase of the menstrual cycle without altering the functional life span of the CL. In contrast, exogenous activin infused systemically caused rapid, premature regression of the CL. Since intraluteal infusion did not alter luteal function, peripheral actions, including suppression of LH (but not FSH) levels, may be implicated in the luteolytic effect of activin.