ER-BETA - IDENTIFICATION AND CHARACTERIZATION OF A NOVEL HUMAN ESTROGEN-RECEPTOR

A novel estrogen receptor (hereinafter referred to as ER beta) was clo ned using degenerate PCR primers, A comparison of the amino acid seque nce of ER beta with the 'classical' ER (ER alpha) shows a high degree of conservation of the DNA-binding domain (96%), and of the ligand-bin ding domain (58%), In contrast, the A/B domain, the hinge region and t he F-domain are not conserved. Northern blot analysis revealed that ER beta is expressed in human thymus, spleen, ovary and testis, Transien t transfections of an ER beta expression construct together with an ER E-based reporter construct in CHO cells clearly demonstrated transacti vation of ER beta by 17 beta-estradiol. In addition, the ER alpha anta gonist ICI-164384 is a potent antagonist for ER beta as well, Interest ingly, the level of transactivation by 17 beta-estradiol is higher for ER alpha than for ER beta, which may reflect suboptimal conditions fo r ER beta at the level of the ligand, responsive element or cellular c ontext.