The purpose of the present study was to determine the parameters of pulsatile gonadotropin secretion in the adult male rat that are regulated by the suppressive feedback influences provided by factors originating in the Leydig cells or by endogenous inhibin, or both. This was achieved by examining the changes in the secretion parameters of FSH and LH that result from selectively destroying the Leydig cells using the toxicant ethane dimethane sulfonate (EDS) or passively iramunoneutralizing endogenous inhibin using high-titer anti a-inhibin subunit serum, or both. Both FSH and LH were secreted in a pulsatile manner in intact male rats as determined using two different pulse-detection methods. Destruction of the Leydig cells with EDS 6 days before sampling significantly increased basal FSH secretion without affecting pulsatile FSH secretion. Injection of anti-inhibin serum into intact (vehicle treated) males 18 h before sampling produced no observable alteration in any parameter of FSH secretion. Either administration of anti-inhibin serum or castration of rats previously treated with EDS induced further significant, selective increases in the basal parameters of FSH secretion, raising mean FSH to levels comparable to those observed in 6-day castrate rats. When examined individually, however, the parameters of mean trough and peak FSH level and mean pulse amplitude remained significantly higher in the 6-day castrate males. In sharp contrast to the selective effects on basal FSH, destruction of the Leydig cells with EDS dramatically elevated all parameters of LH secretion to levels comparable to those observed in similarly timed castrate rats. Neither immunoneutralization of endogenous inhibin nor castration of EDS-treated rats 18 h before sampling caused any further alteration in any parameter of LH secretion. The results from these studies demonstrate that the Leydig cell provides all of the suppressive influence of the testes on LH secretion and a major portion of the suppressive influence over FSH secretion. This influence is exerted through a suppression of all parameters of LH secretion, but through a selective suppression of basal FSH secretion parameters. Collectively, the results suggest that the Leydig cell-derived influences suppress those parameters of gonadotropin secretion that are mediated by LHRH, acting, at least in part, through a suppression of pituitary sensitivity to LHRH. In the absence of the Leydig cells, endogenous inhibin can be demonstrated to also suppress basal FSH secretion in the adult male rat. The similar increases in FSH secretion induced by immunoneutralization of inhibin in EDS-treated rats and castration of EDS-treated rats suggest that the influences provided by the Leydig cells and endogenous inhibin together account for the total suppressive control exerted by the testes over FSH secretion. The larger increases observed in the individual parameters of mean trough and peak levels and mean pulse amplitude in the 6-day castrate rats are most likely the result of the combined loss of inhibin and the Leydig cell influence for the full 6-day period; however, the possibility of an additional Sertoli cell factor that has a minor suppressive effect on FSH secretion cannot be excluded. © 1990 by The Endocrine Society.
