title: Steroid receptor coactivator-1 mediates estrogenic actions to prevent body weight gain in female mice.
abstract: Estrogen receptor-α (ERα) expressed by hypothalamic proopiomelanocortin and steroidogenic factor-1 neurons largely mediates the antiobesity effects of estrogens in females. However, the critical molecular events that are coupled to ERα and mediate estrogenic effects on energy balance remain unknown. In the current study, we demonstrated that steroid receptor coactivator-1 (SRC1), a nuclear receptor coactivator, is abundantly expressed by both proopiomelanocortin and steroidogenic factor-1 neurons. We further showed that central administration of an ERα agonist, propyl pyrazole triol, acutely increases physical interaction between SRC1 and ERα in the hypothalamus. Finally, we demonstrated that the effects of estrogens on energy homeostasis are significantly blunted in female mice lacking SRC1 globally. Collectively our results indicate that SRC1 is functionally required to mediate the antiobesity effects of estrogen-ERα signals.
authors.affiliation: Children’s Nutrition Research Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77479, USA.
authors.forename: Liangru
authors.initials: L
authors.lastname: Zhu
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Yang
authors.forename: Pingwen
authors.initials: P
authors.lastname: Xu
authors.forename: Fang
authors.initials: F
authors.lastname: Zou
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yan
authors.forename: Lan
authors.initials: L
authors.lastname: Liao
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism*; D010636:Phenols; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D010636:Phenols; D011720:Pyrazoles; D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D011333:Pro-Opiomelanocortin; D056920:Nuclear Receptor Coactivator 1