Estrogen receptor-beta, referred to as ESR2, is a member of the superfamily of nuclear receptors, which can transduce extracellular signals into transcriptional responses. This gene is mapped to 14q and comprises 8 exons spanning approximately 40 kb. ESR2 is expressed in multiple tissues, including developing spermatids of the testis and in ovarian granulosa cells1. ESR-beta is homologous to the previously identified ESR-alpha and has an overlapping but nonidentical tissue distribution. The DNA-binding domain of ESR-beta is 96% conserved compared to ESR, and the ligand-binding domain shows 58% conserved residues. ESR-beta is expressed in human thymus, spleen, ovary, and testis2. Rat ESR-beta is expressed in rat prostate and ovary and is homologous to rat ESR (95% conserved DNA-binding domain; 55% conserved ligand-binding domain)3. ESR2 mRNA was coexpressed with ESR1 and its splice variants in 60% of prolactinomas, 100% of mixed growth hormone /prolactin tumors, and 29% of gonadotroph tumors. ESR2 gene expression was not limited to ESR1-positive tumor subtypes, however, and was also found in 100% of null cell tumors, 80% of somatotroph tumors, and 60% of corticotroph tumors4.