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 micrograms intravenous (i.v.) 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 micrograms subcutaneous (SC) or intramuscular (IM) administered to castrate monkeys (n = 3), achieved and maintained normal serum inhibin levels for 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Christensen
R B
RB
Endocrinology Section, Veterans Affairs Medical Center, Seattle, Washington 98108.
Forage
R G
RG
Steiner
R A
RA
Bremner
W J
WJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000097:blood* / Q000502:physiology; D006207:Half-Life; D006801:Humans; D007265:Inhibins / Q000097:blood / Q000493:pharmacokinetics*; D007986:Luteinizing Hormone / Q000097:blood* / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D009919:Orchiectomy; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone