Hormonal regulation of nuclear type II estrogen binding sites in the dorsolateral prostate of noble rats.

We previously demonstrated that simultaneous treatment of Noble (NBL) rats with estradiol (E2) and testosterone (T) for 16 weeks induces a proliferative response selectively in the dorsolateral prostates (DLP) of all treated animals [1, 2]. The unique sensitivity of rat DLP to the conjoint androgen-estrogen-induced mitogenic action may be attributable to the presence of a moderate affinity, high capacity, nuclear estrogen binder (type II sites) found exclusively in this prostatic lobe [2, 3]. Little is known about whether prostatic type II site levels are under hormonal regulation. The aim of this study is to determine whether testicular steroids play a role in regulating the basal and/or induced levels of type II site expression in rat DLP. In the first experiment, rats were castrated and immediately treated with 5 alpha-dihydrotestosterone (DHT) and/or E2 for 6 weeks to determine whether these steroids, separately or jointly, could sustain DLP type II site levels in castrates. Treatments of castrated rats with DHT and DHT+E2 were found to be effective in maintaining DLP type II site levels and gland wet weights at values close to those found in intact untreated controls, while treatments with E2 failed to maintain these parameters at levels observed in intact animals. In the second experiment, intact rats were treated with an androgen (T or DHT) or E2, alone or in combination, for 16 weeks to ascertain which hormonal regimen could induce a higher level of type II site expression in the DLP. Treatments of rats with an androgen (T or DHT) or E2 alone did not change DLP type II site levels even though T treatment caused a slight increase in gland weight, while E2 treatment induced prostatic atrophy. Contrary to single hormone treatments, combined T + E2 and DHT+E2 treatments were effective in inducing a doubling of type II sites and increases in wet weight of the DLPs. These data indicate that testicular androgen is the primary factor responsible for maintaining a basal level of type II site expression in rat DLP, while conjoint androgenic-estrogenic action is needed for the induction of a higher level of type II site expression in the tissue.