EFFECTS OF CASTRATION AND RECOMBINANT HUMAN INHIBIN ADMINISTRATION ONCIRCULATING LEVELS OF INHIBIN AND GONADOTROPINS IN ADULT MALE MONKEYS

Inhibin has been suggested to play a role in gonadal feedback regulati on of follicle-stimulating hormone (FSH) secretion; however, neither t he half-life nor the time course of action of recombinant inhibin has been reported in any primate species. We sought to determine the disap pearance half-life of circulating endogenous inhibin following castrat ion in adult male monkeys, Macaca fascicularis, and to determine the h alf-life of administered recombinant human inhibin A and its effect on bioactive FSH and luteinizing hormone (LH) levels in castrate monkeys . Endogenous inhibin fell from 8,122 +/- 2,077 U/L (mean +/- SEM, n = 5) prior to castration to 383 +/- 84 U/L at 24 hours and 269 +/- 44 U/ L at day 21 (P < 0.05 at 24 hours vs. day 21)(detection limit of assay 234 U/L). The early phase half-life of endogenous inhibin was 34 minu tes (between 8 and 60 minutes) and a later phase half-life of 75 minut es was observed between 1 and 4 hours following castration. Recombinan t inhibin exhibited a 14-minute early phase half-life between 8 and 60 minutes following the 5 mu g intravenous (IV) recombinant inhibin dos e, and a later phase half-life of 70 minutes between 1 and 4 hours in castrate monkeys (n = 3). Serum inhibin levels were maintained within or above the precastration range for 15 minutes. Single dose recombina nt inhibin, 100 mu g subcutaneous (SC) or intramuscular (IM) administe red to castrate monkeys (n = 3), achieved and maintained normal serum inhibin levels for 6 hours. When bioactive FSH and LH responses were a ssessed by either the posttreatment nadir value or the area under the curve of the posttreatment values relative to the pretreatment baselin e, no significant effect was observed following the 0-, 0.5-, 5-, or 5 0-mu g IV recombinant inhibin dosages over the 10-hour sampling period . We conclude first that virtually all circulating inhibin is produced by the testis in male monkeys. Second, recombinant inhibin has a shor t early phase half-life in monkeys, similar to that of endogenous inhi bin. Third, inhibin's putative effect of suppressing FSH secretion may require more prolonged replacement in long-term castrate monkeys. Fou rth, IM or SC administration or recombinant inhibin appears to be a su itable means of achieving replacement serum inhibin levels in castrate monkeys.