HUMAN RECOMBINANT INHIBIN-A AND TESTOSTERONE ACT DIRECTLY AT THE PITUITARY TO SUPPRESS PLASMA-CONCENTRATIONS OF FSH IN CASTRATED RAMS

The roles of inhibin and testosterone in the negative feedback control of the secretion of FSH were explored in experiments using castrated rams administered human recombinant inhibin A (hr-inhibin) and testosterone propionate (TP). Two experiments were conducted in the non-breeding season. In experiment 1, two groups of long-term castrated rams (wethers) were treated with an i.v. injection of either vehicle or hr-inhibin in two doses (25 and 50 mug) given 2 weeks apart. Plasma concentrations of FSH, measured by radioimmunoassay, were suppressed significantly (P<0.01) and equally by both doses of hr-inhibin with a mean (+/- S.E.M.) maximal suppression of FSH of 19.9 +/- 2.60% occurring 6 10 h after injection. In experiment 2, hypothalamopituitary disconnected (HPD) wethers given 125 ng gonadotrophin-releasing hormone (GnRH) every 2 h, were treated with vehicle or 25 or 50 mug hr-inhibin before or after treatment (32 mg/day) with TP. A cross-over design was used so that each wether was treated with vehicle and hr-inhibin. Treatment with TP significantly (P<0.001) suppressed plasma concentrations of FSH by 56%. Both doses of hr-inhibin were similarly effective in significantly (P<0.05) suppressing plasma concentrations of FSH causing a mean suppression of 31.1 +/- 5.60% 6-10 h after injection. The suppressive effect of hr-inhibin was significantly (P<0.05) increased when the wethers were treated with TP to a mean suppression of 50.7 +/- 5.6% 6-10 h after injection. These data indicate that both inhibin and testosterone exert negative feedback control on FSH secretion in rams and that the suppressive effects of inhibin may be enhanced by testosterone. Furthermore, both inhibin and testosterone acted directly on the pituitary to suppress FSH secretion in rams. The inhibition of FSH by a direct pituitary action of testosterone in this study is at variance with our previous findings with HPD wethers during the breeding season when it was shown that testicular steroids have minimal feedback effects at this level. These discrepancies suggest that the sensitivity of the pituitary to negative feedback by testicular steroids may change with the breeding season independent of an input from the hypothalamus. Finally, the greater suppressive effects of hr-inhibin in HPD wethers in experiment 2 compared with the hypothalamo-pituitary intact wethers in experiment 1 suggests that the sensitivity of the pituitary to inhibin may be increased by limiting the GnRH stimulus to the pituitary.