title: Contribution of a membrane estrogen receptor to the estrogenic regulation of body temperature and energy homeostasis.
abstract: The hypothalamus is a key region of the central nervous system involved in the control of homeostasis, including energy and core body temperature (Tc). 17β-Estradiol (E2) regulates Tc, in part, via actions in the basal hypothalamus and preoptic area. E2 primarily controls hypothalamic functions via the nuclear steroid receptors, estrogen receptor α/β. However, we have previously described an E2-responsive, Gq-coupled membrane receptor that reduces the postsynaptic inhibitory γ-aminobutyric acid-ergic tone and attenuates postovariectomy body weight gain in female guinea pigs through the administration of a selective Gq-mER ligand, STX. To determine the role of Gq-mER in regulating Tc, energy and bone homeostasis, ovariectomized female guinea pigs, implanted ip with temperature probes, were treated with STX or E2 for 7-8 wk. Tc was recorded for 4 wk, whereas food intake and body weight were monitored daily. Bone density and fat accumulation were determined postmortem. Both E2 and STX significantly reduced Tc in the females compared with controls. STX, similar to E2, reduced food intake and fat accumulation and increased tibial bone density. Therefore, a Gq-mER-coupled signaling pathway appears to be involved in maintaining homeostatic functions and may constitute a novel therapeutic target for treatment of hypoestrogenic symptoms.
authors.affiliation: Department of Physiology and Pharmacology, Mail Code L334, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Roepke
authors.forename: Martha A
authors.initials: MA
authors.lastname: Bosch
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rick
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lee
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Wagner
authors.forename: Dana
authors.initials: D
authors.lastname: Seidlova-Wuttke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wuttke
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: Oline K
authors.initials: OK
authors.lastname: Rønnekleiv
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Kelly
mesh_terms: D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism* / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism / Q000502:physiology; D006168:Guinea Pigs; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008253:Macaca mulatta; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
chemical_list: C553231:2-(4-hydroxyphenyl)-3-phenylpent-2-enoic acid (4-(2-dimethylaminoethoxy)phenyl)amide; D000178:Acrylamides; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol; D043802:GTP-Binding Protein alpha Subunits, Gq-G11