A novel estrogen receptor (hereinafter referred to as ERβ) was cloned using degenerate PCR primers. A comparison of the amino acid sequence of ERβ with the ‘classical’ ER (ERα) shows a high degree of conservation of the DNA-binding domain (96%), and of the ligand-binding domain (58%). In contrast, the A/B domain, the hinge region and the F-domain are not conserved. Northern blot analysis revealed that ERβ is expressed in human thymus, spleen, ovary and testis. Transient transfections of an ERβ expression construct together with an ERE-based reporter construct in CHO cells clearly demonstrated transactivation of ERβ by 17β-estradiol. In addition, the ERα antagonist ICI-164384 is a potent antagonist for ERβ as well. Interestingly, the level of transactivation by 17β-estradiol is higher for ERα than for ERβ, which may reflect suboptimal conditions for ERβ at the level of the ligand, responsive element or cellular context.
