title: GPR30 mediates anorectic estrogen-induced STAT3 signaling in the hypothalamus.
abstract: OBJECTIVE
  Estrogen plays an important role in the control of energy balance in the hypothalamus. Leptin-independent STAT3 activation (i.e., tyrosine(705)-phosphorylation of STAT3, pSTAT3) in the hypothalamus is hypothesized as the primary mechanism of the estrogen-induced anorexic response. However, the type of estrogen receptor that mediates this regulation is unknown. We investigated the role of the G protein-coupled receptor 30 (GPR30) in estradiol (E2)-induced STAT3 activation in the hypothalamus.
  
  
  METHODS
  Regulation of STAT3 activation by E2, G-1, a specific agonist of GPR30 and G-15, a specific antagonist of GPR30 was analyzed in vitro and in vivo. Effect of GPR30 activation on eating behavior was analyzed in vivo.
  
  
  RESULTS
  E2 stimulated pSTAT3 in cells expressing GPR30, but not expressing estrogen receptor ERα and ERβ. G-1 induced pSTAT3, and G-15 inhibited E2-induced pSTAT3 in primary cultures of hypothalamic neurons. A cerebroventricular injection of G-1 increased pSTAT3 in the arcuate nucleus of mice, which was associated with a decrease in food intake and body weight gain.
  
  
  CONCLUSIONS
  These results suggest that GPR30 is the estrogen receptor that mediates the anorectic effect of estrogen through the STAT3 pathway in the hypothalamus.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Obin
authors.initials: O
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.affiliation: Division of Metabolic Disease, Department of Biomedical Science, National Institutes of Health, Osong, Korea.
authors.forename: Insook
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Mijung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Somin
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: So Ra
authors.initials: SR
authors.lastname: Oh
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea. Electronic address: ahnys@yuhs.ac.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. Electronic address: kimhoon@yuhs.ac.
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000855:Anorexia / Q000503:physiopathology*; D001483:Base Sequence; D017931:DNA Primers; D004967:Estrogens / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology*; D051379:Mice; D011960:Receptors, Estrogen / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017931:DNA Primers; D004967:Estrogens; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Estrogen; Food intake; G protein-coupled receptor 30; Hypothalamus; STAT3