Effects of castration and recombinant human inhibin administration on circulating levels of inhibin and gonadotropins in adult male monkeys

Inhibin has been suggested to play a role in gonadal feedback regulation of follicle‐stimulating hormone (FSH) secretion; however, neither the half‐life nor the time course of action of recombinant inhibin has been reported in any primate species. We sought to determine the disappearance half‐life of circulating endogenous inhibin following castration in adult male monkeys, Macaca fascicularis, and to determine the half‐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 minutes (between 8 and 60 minutes) and a later phase half‐life of 75 minutes was observed between 1 and 4 hours following castration. Recombinant inhibin exhibited a 14‐minute early phase half‐life between 8 and 60 minutes following the 5 μg intravenous (IV) recombinant inhibin dose, 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 recombinant inhibin, 100 μg subcutaneous (SC) or intramuscular (IM) administered to castrate monkeys (n = 3), achieved and maintained normal serum inhibin levels for 6 hours. When bioactive FSH and LH responses were assessed by either the posttreatment nadir value or the area under the curve of the posttreatment values relative to the pretreatment baseline, no significant effect was observed following the 0‐, 0.5‐, 5‐, or 50‐μg 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 short early phase half‐life in monkeys, similar to that of endogenous inhibin. Third, inhibin's putative effect of suppressing FSH secretion may require more prolonged replacement in long‐term castrate monkeys. Fourth, IM or SC administration or recombinant inhibin appears to be a suitable means of achieving replacement serum inhibin levels in castrate monkeys.