GONADOTROPIN-SUPPRESSING ACTIVITY OF HUMAN RECOMBINANT INHIBIN IN THEMALE-RAT IS AGE-DEPENDENT

We have examined the age-dependent effects of human recombinant inhibi n A (hrI) on gonadotropln levels in intact male rats. A single s.c. in jection of hrI in the dose range 6.25-100 ng/g BW resulted in a signif icant 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 less than or equal to 20 days old had no significant effect on serum FSH levels. similarly no e ffect 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 w as observed on serum LH levels except in 40-day old rats, which exhibi ted a consistent and significant reduction at the higher (25-100 ng/g) doses of inhibin. Serum inhibin levels G h after the injection were n ot significantly altered at any dose in young animals (less than or eq ual to 30 days); however, in older animals (40, 50, and 91 days) there was a significant elevation in circulating inhibin levels at the high er doses, strongly suggesting an age-related change in clearance. Test icular inhibin levels were not affected by administration of the exoge nous material except at the highest dose (100 ng/g) in the oldest anim als (91 days), when an approximately 30% reduction in both the concent ration and the total content of inhibin was observed. The data clearly demonstrate that the effect of hrI on serum gonadotropins is age depe ndent and that changes in clearance may contribute to the period durin g which circulating inhibin levels are elevated postinjection.