Estrogen enhancement of androgen‐responsive gene expression in hormone‐induced hyperplasia in the ventral prostate of F344 rats

It has been postulated that, in addition to the crucial role of androgens, estrogens may be involved in development of prostate hyperplasia and cancer. In rats, combined administration of estrogen and androgen synergistically increases ventral prostate weight, and continued treatment results in the development of glandular hyperplasia. Prostate adenocarcinoma can be induced by chemical carcinogens in rats, and estrogen given together with an androgen generally shortens the latent period or increases the incidence and/or multiplicity of carcinomas. However, the mechanisms responsible for these synergistic effects of estrogen and androgen are poorly understood. In the present study, we examined the combined effects of 17β‐estradiol (E2) and testosterone (T) on gene expression in an early stage of prostate hyperplasia in an F344 rat model. ERα expression, which has been suggested to contribute to development of prostatic hyperplasia, was increased by the combined treatment with T and E2, while it was suppressed by T alone. Expression levels of two androgen‐responsive genes, probasin and kallikrein S3, were increased in the ventral prostate of rats treated with T plus E2 for 4 weeks in a dose‐dependent manner, while short‐term treatment did not alter the expression. These results suggested that enhancing effects of E2 on transcription of androgen‐responsive genes, as well as an increased level of ERα may play roles in the synergistic effects of E2 on T‐induced prostate hyperplasia.