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ERß1 and the ERß2 Splice Variant (ERßcx/ß2) Are Expressed in Distinct Cell Populations in the Adult Human Testis

Medical Research Council Human Reproductive Sciences Unit (P.T.K.S., M.R.M., S.M., D.S.I., R.M.S., G.A.S.), Centre for Reproductive Biology, Edinburgh EH3 9ET, United Kingdom; and School of Biological & Molecular Sciences (N.P.G., L.R.E.), Oxford Brookes University, Gypsy Lane Campus, Headington, Oxford OX3 0PB, United Kingdom

Address all correspondence and requests for reprints to: Dr. Philippa T. K. Saunders, Medical Research Council Human Reproductive Sciences Unit, Center for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9ET, United Kingdom. E-mail: . p.saunders{at}ed.ac.uk

Abstract

Estrogens can regulate germ cell function. Estrogen action is mediated via high affinity ERs; two subtypes (ER and ERß) have been identified. We have shown previously that ERß is expressed in nuclei of multiple human testicular cells. A variant isoform of human (h) ERß (hERßcx/2), formed by alternative splicing, has been identified in testicular cDNA libraries by two laboratories. The present study examined the expression of wild-type (ERß1) and variant (ERß2) ß receptors in human testes by 1) RT-PCR with isoform specific primers, and 2) single and double immunohistochemistry using monoclonal antibodies raised against peptides unique to the C termini of hERß1 and hERß2. PCR products specific for ERß1 and ERß2 were amplified from cDNA pools prepared from human testes and granulosa cells. On Western blots, the anti-ERß1 monoclonal antibody bound to recombinant ERß1 and the anti-ERß2 monoclonal to recombinant hERß2. Neither bound to the other ERß isoform nor to recombinant ER. ERß1 and ERß2 proteins were both detected in human testis. Immunoexpression of ERß1 was most intense in pachytene spermatocytes and round spermatids, whereas low levels of expression were detected in Sertoli cells, spermatogonia, preleptotene, leptotene, zygotene, and diplotene spermatocytes. Highest levels of expression of ERß2 protein were detected in Sertoli cells and spermatogonia with low/variable expression in preleptotene, pachytene, and diplotene spermatocytes. No immunostaining was detected in elongating spermatids. Most interstitial cells expressed more ERß2 than ERß1. It is speculated that the cells most susceptible to modulation by estrogenic ligands are round spermatids in which levels of expression of ERß1 are high. In contrast, expression of ERß2, an isoform that may act as a dominant negative inhibitor of ER action, in Sertoli cells and spermatogonia, could protect these cells from adverse effects of estrogens.

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