Immunocytochemical localization of estrogen receptors alpha and beta in the human reproductive organs.

To better define the role of estrogens in reproductive functions, we have proceeded to the immunocytochemical localization of the estrogen receptor (ER) subtypes, ERalpha and the recently discovered ERbeta+, in human reproductive tissues. In the ovary, ERbeta+ immunoreactivity was found in nuclei of granulosa cells of growing follicles at all stages from primary to mature follicles, interstitial gland, and germinal epithelium cells. Nuclear staining for ERalpha occurred in thecal, interstitial gland, and germinal epithelium cells. In the uterus, strong ERalpha immunoreactivity was detected in nuclei of epithelial, stromal, and muscle cells. Similar localization was obtained for ERbeta+, although the staining was much weaker. In the vagina, only ERalpha could be detected; a nuclear reaction was observed in deep layers of the stratified epithelium as well as in stromal and muscle cells. In the mammary gland, both ER subtypes were observed in epithelial and stromal cells. In the testis, ERbeta+ was detected in nuclei of Sertoli and Leydig cells, whereas ERalpha immunoreactivity was only observed in Leydig cells, with no tubular labeling. In the efferent ducts, only ERbeta+ could be detected, whereas neither ERbeta+ nor ERalpha could be found in the epididymis. In the prostate, ERbeta+ nuclear immunolabeling was observed in both basal and secretory cells in alveoli as well as in stromal cells, whereas ERalpha could not be detected. The present results demonstrate that there is a cell-specific localization for each of the ER subtypes in the majority of the reproductive organs studied. Moreover, they contribute to establish the exact sites of action of estrogens in male and female human reproductive systems.