Human oestrogen receptors: differential expression of ERalpha and beta and the identification of ERbeta variants

Two structurally related subtypes of oestrogen receptor (ER), known as alpha (ERalpha, NR3A1) and beta (ERbeta, NR3A2) have been identified. ERbeta mRNA and protein have been detected in a wide range of tissues including the vasculature, bone, and gonads in both males and females, as well as in cancers of the breast and prostate. In many tissues the pattern of expression of ERbeta is distinct from that of ERalpha. A number of variant isoforms of the wild type beta receptor (ERbeta1), have been identified. In the human these include: (1) use of alternative start sites within the mRNA leading to translation of either a long (530 amino acids, hERbeta1L) or a truncated form (487aa hERbeta1s); (2) deletion of exons by alternative splicing; (3) formation of several isoforms (ERbeta2-beta5) due to alternative splicing of exons encoding the carboxy terminus (F domain). We have raised monoclonal antibodies specific for hERbeta1 as well as to three of the C terminal isoforms (beta2, beta4 and beta5). Using these antibodies we have found that ERbeta2, beta4 and beta5 proteins are expressed in nuclei of human tissues including the ovary, placenta, testis and vas deferens. In conclusion, in addition to the differential expression of full length ERalpha and ERbeta a number of ER variant isoforms have been identified. The impact of the expression of these isoforms on cell responsiveness to oestrogens may add additional complexity to the ways in which oestrogenic ligands influence cell function. (C) 2002 Elsevier Science Inc. All rights reserved.