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GPR30 mediates anorectic estrogen-induced STAT3 signaling in the hypothalamus

 Obin Kwon  ;  Eun Seok Kang  ;  Insook Kim  ;  Sora Shin  ;  Mijung Kim  ;  Somin Kwon  ;  So Ra Oh  ;  Young Soo Ahn  ;  Chul Hoon Kim 
 Metabolism: Clinical and Experimental, Vol.63(11) : 1455-1461, 2014 
Journal Title
 Metabolism: Clinical and Experimental 
Issue Date
Animals ; Anorexia/physiopathology* ; Base Sequence ; DNA Primers ; Estrogens/physiology* ; HeLa Cells ; Humans ; Hypothalamus/physiopathology* ; Mice ; Receptors, Estrogen/physiology* ; Receptors, G-Protein-Coupled/physiology* ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/physiology*
Estrogen ; Food intake ; G protein-coupled receptor 30 ; Hypothalamus ; STAT3
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. MATERIALS/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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kwon, O Bin(권오빈)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Shin, So Ra(신소라)
Ahn, Young Soo(안영수)
Oh, So Ra(오소라)
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