Gonadotropin-suppressing activity of human recombinant inhibin in the male rat is age dependent.
We have examined the age-dependent effects of human recombinant inhibin A (hrI) on gonadotropin levels in intact male rats. A single s.c. injection of hrI in the dose range 6.25-100 ng/g BW resulted in a significant and consistent decrease (20-40%) in serum FSH measured 6 h later, at the higher (50 and 100 ng/g) doses, in animals 25-91 days of age. Administration of the same doses in animals < or = 20 days old had no significant effect on serum FSH levels. Similarly, no effect of hrI (100 ng/g) on serum FSH levels was observed in 15-day-old rats when FSH levels were monitored from 1 to 8 h. No effect of hrI was observed on serum LH levels except in 40-day-old rats, which exhibited a consistent and significant reduction at the higher (25-100 ng/g) doses of inhibin. Serum inhibin levels 6 h after the injection were not significantly altered at any dose in young animals (< or = 30 days); however, in older animals (40, 50, and 91 days) there was a significant elevation in circulating inhibin levels at the higher doses, strongly suggesting an age-related change in clearance. Testicular inhibin levels were not affected by administration of the exogenous material except at the highest dose (100 ng/g) in the oldest animals (91 days), when an approximately 30% reduction in both the concentration and the total content of inhibin was observed. The data clearly demonstrate that the effect of hrI on serum gonadotropins is age dependent and that changes in clearance may contribute to the period during which circulating inhibin levels are elevated postinjection.
Wreford
N G
NG
Institute for Reproduction and Development, Monash University, Clayton, Victoria, Australia.
O'Connor
A E
AE
de Kretser
D M
DM
D000375:Aging / Q000502:physiology*; D000818:Animals; D005640:Follicle Stimulating Hormone / Q000097:blood*; D006801:Humans; D007265:Inhibins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000378:metabolism
D011994:Recombinant Proteins; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone