Depletion of the cytoplasmic estrogen receptor in gonadotropin-desensitized testes.

Recent studies have shown that hCG stimulates 17 beta-estradiol production in the testis, and a possible role for 17 beta-estradiol in hCG-induced desensitization of testosterone synthesis has been suggested. These studies were initiated to examine the testicular content of cytoplasmic estrogen receptor in relation to hCG-induced desensitization of testosterone production 24 h and 5 days after a sc injection of hCG. Twenty-four hours after the injection of 30, 300, and 3000 IU hCG, pronounced (82-88%) depletion of the cytoplasmic estrogen receptor was observed, while a 3-IU dose elicited a 41% depletion. A concomitant desensitization to hCG stimulation in vitro was observed after the injection of 30, 300, and 3000 IU hCG, as reflected by a lack of stimulation of testosterone production above that in matched controls. Testicular 17 beta-estradiol levels rose significantly after the injection of 300 or 3000 IU hCG. Five days after the injection of hCG, full replenishment of the cytoplasmic estrogen receptor had occurred in the 3- and 30-IU dose groups, while partial replenishment (22-56% depletion) had occurred with the 300- and 3000-IU dose groups. Only the 3000-IU dose group remained desensitized to hCG stimulation in vitro at this time point. Results indicated that occupancy by endogenous 17 beta-estradiol was not a factor, thus suggesting a true receptor depletion phenomenon. These results demonstrate that hCG-induced desensitization of testicular steroidogenesis is accompanied by depletion of the cytoplasmic estrogen receptor. Further, replenishment of the estrogen receptor at 5 days was accompanied by a return of the testicular response to hCG.