Immunolocalisation of oestrogen receptor beta in human tissues

Oestrogens exert their actions via specific nuclear protein receptors that are members of the steroid/thyroid receptor superfamily of transcription factors. Recently, a second oestrogen receptor (ER beta) has been cloned, and using reverse transcription-PCR and immunohistochemistry it has been shown to have a wide tissue distribution in the rat that is distinct from the classical oestrogen receptor, ER alpha. Using commercial polyclonal antisera against peptides specific to human ER beta, we have determined the sites of ER beta expression in archival and formalin-fixed human tissue and compared its expression with that of ER alpha. ER beta was localised to the cell nuclei of a wide range of normal adult human tissues including ovary, Fallopian tube, uterus, lung, kidney, brain, heart, prostate and testis. In the ovary, ER beta was present in multiple cell types including granulosa cells in small, medium and large follicles, theca and corpora lutea, whereas ER alpha was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. in the endometrium, both ER alpha and ER beta were observed in luminal epithelial cells and in the nuclei of stromal cells but, significantly, ER beta was weak or absent from endometrial glandular epithelia. Epithelial cells in most male tissues including the prostate, the urothelium and muscle layers of the bladder, and Sertoli cells in the testis, were also immunopositive for ER beta. Significant ER beta immunoreactivity was detected in most areas of the brain, with the exception of the hippocampus - a tissue that stained positively for ER alpha. In conclusion, the almost ubiquitous immunohistochemical localisation of ER beta indicates that ER beta may play a major role in the mediation of oestrogen action. The differential expression of ER alpha and ER beta in some of these tissues suggests a more complex control mechanism in oestrogenic potential than originally envisioned.