ABSTRACT
The treatment of Sprague-Dawley rats for 16 weeks with testosterone [T] and estradiol-17 beta [E2] induces prostatic dysplasia by 80%. The combined hormonal treatment also induces hyperprolactinemia. The aim of this study was to investigate whether the dual hormone action is mediated via E2-induced hyperprolactinemia. Bromocriptine [Brc] was used to suppress pituitary prolactin [PRL] release. Serum PRL levels were lowered from values of 329 +/- 41 ng/ml in T + E2 treated rats to 35 +/- 9 ng/ml in Brc co-treated animals and this were comparable to PRL levels in untreated rats. Brc not only blocked the hyperprolactinemia but also blocked the dysplasia induced by T + E2 treatment. However, it remains to be defined whether estrogen exerts direct trophic effects, independent of PRL induction, on the rat prostate and thereby participates in the development of dysplasia in the prostate. To address this question, we used ICI 182, 780 [ICI] to antagonize the action of estrogen at the tissue level in T + E2- treated rats. Initially, we used ICI to block the E2 local effect on the prostate but surprisingly, we observed that ICI was able to block hyperprolactinemia and significantly decrease the number and percentage of the prostatic dysplasia in the rates treated with T + E2. These findings indicate that prostatic dysplasia is mediated through a PRL-dependent as well as PRL-independent mechanisms and suggest a new action for ICI to block the hyperprolactinemia