title: Regulation of gene expression by 17β-estradiol in the arcuate nucleus of the mouse through ERE-dependent and ERE-independent mechanisms.
abstract: 17β-Estradiol (E2) modulates gene expression in the hypothalamic arcuate nucleus (ARC) to control homeostatic functions. In the ARC, estrogen receptor (ER) α is highly expressed and is an important contributor to E2's actions, controlling gene expression through estrogen response element (ERE)-dependent and -independent mechanisms. The objective of this study was to determine if known E2-regulated genes are regulated through these mechanisms. The selected genes have been shown to regulate homeostasis and have been separated into three subsections: channels, receptors, and neuropeptides. To determine if ERE-dependent or ERE-independent mechanisms regulate gene expression, two transgenic mouse models, an ERα knock-out (ERKO) and an ERα knock-in/knock-out (KIKO), which lacks a functional ERE binding domain, were used in addition to their wild-type littermates. Females of all genotypes were ovariectomized and injected with oil or estradiol benzoate (E2B). Our results suggest that E2B regulates multiple genes through these mechanisms. Of note, Cacna1g and Kcnmb1 channel expression was increased by E2B in WT females only, suggesting an ERE-dependent regulation. Furthermore, the NKB receptor, Tac3r, was suppressed by E2B in WT and KIKO females but not ERKO females, suggesting that ERα-dependent, ERE-independent signaling is necessary for Tac3r regulation. The adrenergic receptor Adra1b was suppressed by E2B in all genotypes indicating that ERα is not the primary receptor for E2B's actions. The neuropeptide Tac2 was suppressed by E2B through ERE-dependent mechanisms. These results indicate that E2B activates both ERα-dependent and independent signaling in the ARC through ERE-dependent and ERE-independent mechanisms to control gene expression.
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Yang
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Mamounis
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Yasrebi
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, USA. Electronic address: ta.roepke@rutgers.edu.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Roepke
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D055879:Gene Knock-In Techniques; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D009419:Nerve Tissue Proteins; D004958:Estradiol
keywords: 17β-Estradiol; Arcuate nucleus; ERα; Ovariectomy