Plasma concentration of ERr 731 metabolite and the pharmacogenomic profiles for ERα/β target genes and bioactive peptides in the hypothalamus of ERr 731-treated rats. (A) Rhaponticin metabolite was detected in the plasma of rats treated orally with 0.3–3 mg/kg/day ERr 731 for 14 days in study 2 and (B) 7 days in study 3. (C) E2 treatment significantly upregulated ERα but not ERβ target genes in the hypothalamus of OVX rats, and the opposite effect was observed for ERr 731. (D) Neither E2 nor ERr 731 modulated the expression of neurotrophic factors; however, an agouti-related peptide Agrp was significantly elevated following the OVX surgery and ERr 731 treatment abolished this response. Individual hypothalamic tissue samples (n = 6) were analyzed by fluorescent quenching (A,B) or qPCR (C,D), and the data were expressed as the mean ± SEM, * p < 0.05 and *** p < 0.001 vs. OVX control.