TARRANT, A.M.*; GREYTAK, S.R.; CALLARD, G.V.; HAHN, M.E.; Woods Hole Oceanographic Institution, MA; Boston University, MA; Boston University, MA; Woods Hole Oceanographic Institution, MA: Estrogen receptor-related receptors in the Atlantic killifish Fundulus heteroclitus: diversity, expression, and estrogen responsiveness

Estrogen receptor-related receptors (ERRs) are a group of nuclear receptors that are phylogenetically related to estrogen receptors. There are three mammalian ERR genes that help to regulate diverse processes, ranging from placental development to maintenance of bone density. In contrast, ERRs are poorly characterized in non-mammalian species. We report the cloning of four ERR cDNAs from killifish, adult tissue expression patterns, and estrogen responsiveness. Phylogenetic analysis indicates that FhERR&alpha is orthologous to the single ERR&alpha identified in mammals, pufferfish and zebrafish. FhERRβa and FhERRβb are co-orthologs of the mammalian ERR&beta. Phylogenetic placement of the fourth killifish ERR gene, tentatively identified as FhERRγb, is less clear. The four ERRs showed distinct mRNA expression patterns in adult tissues. FhERR&alpha was broadly expressed. FhERRβa was expressed at apparently low levels in eye and brain. FhERRβb was expressed more broadly in gonad, eye, brain and kidney. FhERRγb was primarily expressed in gill and heart. Distinct expression patterns of FhERRβa and FhERRβb are consistent with subfunctionalization of ERR&beta paralogs. Induction of ERR&alpha mRNA by exogenous estrogen has been reported in some mammalian tissues. In adult male killifish, ERR expression was not significantly affected by estradiol, but there was a trend toward induction (3-5 fold) of ERR&alpha in heart. Together our results show that killifish contain additional ERR genes relative to mammals, including ERR&beta paralogs, which may facilitate determination of ERR gene functions. Funding provided by Superfund Basic Research Program (P42ES07381) and NRSA (NIEHS/NIH 1 F32 ES013642-01).