title: Ablation of estrogen receptor alpha (ERalpha) prevents upregulation of POMC by leptin and insulin.
abstract: Diabetic Akita male mice are more hyperphagic because of downregulation of proopiomelanocortin (POMC) caused by hypoleptinemia. We investigated the role of estrogen receptor alpha (ERalpha) in the regulation of the hypothalamic POMC in females. ERaKOAkt mice consumed 30% greater food (g/3 weeks) than the Akita diabetic controls. Ovariectomized diabetic (AFO) and nondiabetic (B6FO) mice had significantly lower food intake and elevated serum leptin levels. ERaKOAkt and ERaKO mice also increased serum leptin concentrations, while hypoinsulinemia was observed in ERaKOAkt and hyperinsulinemia in ERaKO mice. RT-PCR showed a significant attenuation of POMC expression in both ERaKOAkt and ERaKO mice, irrespective of the elevated leptin serum levels or hyperinsulinemia, while elevated serum leptin levels in AFO and B6FO mice upregulated POMC gene expression. These results indicate that ERalpha plays an essential role in leptin- and insulin-stimulated upregulation of the POMC gene. This action of ERalpha is likely mediated in a ligand-independent manner.
authors.affiliation: Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo, Kyoto 606-8501, Japan.
authors.forename: Michi
authors.initials: M
authors.lastname: Hirosawa
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Minata
authors.forename: Kouji H
authors.initials: KH
authors.lastname: Harada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hitomi
authors.forename: Andree
authors.initials: A
authors.lastname: Krust
authors.forename: Akio
authors.initials: A
authors.lastname: Koizumi
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D006963:Hyperphagia / Q000235:genetics*; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D020738:Leptin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D047628:Estrogen Receptor alpha; D007328:Insulin; D020738:Leptin; D011333:Pro-Opiomelanocortin