Leydig cell desensitization by human chorionic gonadotropin does not occur in the human fetal testis

In vivo data concerning human fetal testicular testosterone production as well as in vitro findings in fetal and neonatal rats suggest that fetal Leydig cells may be capable of responding to gonadotropins and secreting testosterone at high levels for prolonged periods, in contrast to adult testes which reportedly become desensitized after high dose gonadotropin administration. To evaluate fetal testicular testosterone production during long term, high dose gonadotropic stimulation, we cultured human, rhesus monkey, and rabbit fetal testes in organ and cell cultures. After 24 h of culture with different concentrations of hCG (0-100 ng/ml, physiological fetal concentrations during human gestation), the fetal testes were still able to respond to a second hCG stimulus (no desensitization). The 24-h incubation with hCG (0-100 ng/ml) also increased the capacity of the cultures to secrete testosterone during a second incubation in a dose-dependent manner even in the absence of hCG (steroidogenic enzyme induction). Furthermore, hCG increased thymidine incorporation into DNA by the human fetal testis. The results of this study substantiate the role of hCG in the regulation of fetal Leydig cells. They suggest that long term effects via nuclear mechanisms (RNA and DNA synthesis) may be important aspects of this regulation, and that fetal Leydig cells are able to respond to sustained concentrations of gonadotropin without being desensitized.