[Novel estrogen receptor: a chance for more specific and safe endocrinological treatment?]

In 1996 Kuiper et al. have cloned a novel member of the nuclear receptor superfamily. The cDNA of clone 29 was isolated from a rat prostate cDNA library. The new receptor was highly homologus to the rat estrogen receptor protein, particularly in the DNA-binding domain. New protein consists of 485 amino acid residues and its molecular weight is 54.2 kDa. Like other steroid receptors, ER beta has six regions, A-F. A novel receptor is expressed in the secretory epithelial cells of the prostate and also in the granulosa cells of the ovary. Differences in the ligand-binding properties and transactivation function on target genes may exist. The tissue distribution and relative level of ER alpha and beta expression seems to be quite different, i.e. moderate to high expression in uterus, testis, pituitary, ovary, kidney, and adrenal for ER alpha and prostate, ovary, lung, bladder, brain, uterus and testis for ER beta. The differences between the receptors subtypes in relative ligand binding affinity and tissue distribution could contribute to the selective action of ER aginists and antagonists in different tissues. These new findings bring up many questions. The most intriguing is how has this second ER eluded investigators for so many years? Perhaps a limited number of estrogen target tissues were screened. The biological significance of the existence of two different ERs is at this moment unclear. Perhaps the existence of two ERs subtypes provides an explanation for the selective actions of estrogens in different target tissues.