Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts

This paper describes three distinct estrogen receptor (ER) subtypes: ER alp ha, ER beta, and a unique type. ER gamma, cloned from a teleost fish, the A tlantic croaker Micropogonias undulatus; the first identification of a thir d type of classical ER in vertebrate species. Phylogenetic analysis shows t hat ER gamma arose through gene duplication from ER beta early in the teleo st lineage and indicates that ER gamma is present in other teleosts. althou gh it has not been recognized as such. The Atlantic croaker ER gamma shows amino acid differences in regions important for ligand binding and receptor activation that are conserved in all other ER gamma s. The three ER subtyp es are genetically distinct and have different distribution patterns in Atl antic croaker tissues. In addition, ER beta and ER gamma fusion proteins ca n each bind estradiol-17 beta with high affinity. The presence of three fun ctional ERs in one species expands the role of ER multiplicity in estrogen signaling systems and provides a unique opportunity to investigate the dyna mics and mechanisms of ER evolution.