Two structurally related subtypes of oestrogen receptor (ER), known as alpha (ER alpha,
NR3A1) and beta (ER beta, NR3A2) have been identified. ER beta 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 ER beta is distinct from that of ER alpha. A
number of variant isoforms of the wild type beta receptor (ER beta 1), 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, hER beta 1L) or a truncated form
(487aa hER beta 1s); (2). deletion of exons by alternative splicing; (3). formation
of several isoforms (ER beta 2-beta 5) due to alternative splicing of exons encoding
the carboxy terminus (F domain). We have raised monoclonal antibodies specific for
hER beta1 as well as to three of the C terminal isoforms (beta2, beta 4 and beta 5).
Using these antibodies we have found that ER beta 2, beta 4 and beta 5 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
ER alpha and ER beta 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.