Synergistic effects of estrogen and androgen on the prostate: effects of estrogen on androgen- and estrogen-receptors, BrdU uptake, immunohistochemical study of AR, and responses to antiandrogens

Abstract

To investigate the synergistic effects of estradiol (E2) and testosterone (T) on prostate growth, castrated Wistar rats were treated with 1 mg/day of T or with 1 mg/day of T and 0.01 mg/day of E2 for 6 weeks. The weight of the prostate in T + E2-treated rats was significantly higher than that in T-treated and normal rats, parallel with the bromodeoxy-uridine (BrdU) labeling index (LI). Nuclear androgen receptor (AR) content in the T + E2 group was significantly higher than that in the T group. But they were lower than that in normal rats. And there were no significant differences between the groups in nuclear estrogen receptor (ER) content. Immunohistochemical studies with the AR antibody revealed positive staining in the prostatic epithelium and stromal cells in the normal, T-treated, and T + E2-treated animals. However, castration led to loss of staining. Response to steroidal antiandrogens was also determined. Antiandrogen treatment abrogated the increases in nuclear AR content and BrdU LI, and prevented immunohistochemical staining. These results suggest that AR and ER, which were measured in this study, were not indicators of prostatic proliferation. We further need to investigate other factors, including other types of receptors, growth factors involved in epithelial-stromal interaction, and so on.