THE TIME-COURSE OF FOLLICLE-STIMULATING-HORMONE SUPPRESSION BY RECOMBINANT HUMAN INHIBIN A IN THE ADULT MALE RHESUS-MONKEY (MACACA-MULATTA)

In higher primates, FSH secretion appears to be regulated by a control system consistent with that described by the classical inhibin hypoth esis. The purpose of the present experiment was to examine the time co urse of inhibin's action to suppress FSH secretion in the intact adult male rhesus monkey. To this end, five adult males implanted with indw elling venous catheters and exhibiting typical episodic patterns of LH and testosterone (T) secretion received a 4-day iv infusion of recomb inant human (rh) inhibin A (832 ng/h.kg) followed, after a 4-week inte rval, by vehicle infusion of similar duration. Changes in circulating FSH concentrations during the inhibin and vehicle infusions were deter mined using a sensitive homologous macaque RIA, whereas enzyme-linked immunosorbent assays were employed to track inhibin A, inhibin B, and inhibin pro-alpha-C levels during the experiment. Normal pulsatile act ivity in the hypothalamic-pituitary-leydig cell axis was confirmed by monitoring changes in circulating concentrations of LH and T in 12-h w indows of sequential blood collection (1200-2400 h; every 20 min) befo re, during, and after the rh inhibin A and vehicle infusions. Although infusion of rh inhibin A, which led to a 12 ng/ml square wave increme nt in circulating levels of this inhibin dimer, produced a marked decl ine in circulating FSH concentrations, significant suppression of the secretion of this gonadotropin was not manifest until 54 h after initi ation of the infusion. Despite the marked decline in FSH secretion dur ing the last 24 h of the 4-day infusion of recombinant hormone, circul ating inhibin B and pro-alpha-C concentrations were maintained at prei nfusion control levels (1 ng/ml). The finding that imposition of an ex aggerated circulating inhibin signal led to suppression of FSH secreti on in the male monkey only after 2 days of exposure to the hormone ind icates that in this species the feedback action of testicular inhibin on FSH secretion is heavily lagged. Moreover, as the decrease in FSH d id not lead to changes in native inhibin secretion, it seems reasonabl e to propose that the FSH-inhibin feedback loop that governs testicula r function in higher primates operates with considerable hysteresis at both the pituitary and gonadal levels. The failure of dramatically el evated inhibin A levels to influence the pulsatile secretion of LH in the monkey reinforces the idea that in this species the pituitary acti on of testicular inhibin is specific for FSH and does not involve modu lation of GnRH receptor levels.