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 ) 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 . Using commercial polyclonal antisera against peptides specific to human ER , we have

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... the sites of ER expression in archival and formalin-fixed human tissue and compared its expression with that of ER . ER 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 was present in multiple cell types including granulosa cells in small, medium and large follicles, theca and corpora lutea, whereas ER was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. In the endometrium, both ER and ER were observed in luminal epithelial cells and in the nuclei of stromal cells but, significantly, ER 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 . Significant ER immunoreactivity was detected in most areas of the brain, with the exception of the hippocampus -a tissue that stained positively for ER . In conclusion, the almost ubiquitous immunohistochemical localisation of ER indicates that ER may play a major role in the mediation of oestrogen action. The differential expression of ER and ER in some of these tissues suggests a more complex control mechanism in oestrogenic potential than originally envisioned.