Modulation of hypothalamic neuronal activity through a novel G-protein-coupled estrogen membrane receptor

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Abstract

Estrogens are involved in the hypothalamic control of multiple homeostatic functions including reproduction, stress responses, energy metabolism, sleep cycles, temperature regulation and motivated behaviors. The actions of 17β-estradiol (E2) in the brain have been attributed to the activation of estrogen receptors α and β, as well as G-protein-coupled or other membrane-associated estrogen receptors. Recently, we have identified a putative membrane-associated estrogen receptor that is coupled to desensitization of GABAB receptors in guinea pig and mouse hypothalamic neurons including proopiomelanocortin (POMC) neurons. We have synthesized a new nonsteroidal compound, STX, which selectively targets the Gαq-coupled phospholipase C-protein kinase C-protein kinase A pathway, and have established that STX is more potent than E2 in mediating this desensitization in an ICI 182,780-sensitive manner in both guinea pig and mouse neurons. Both E2 and STX are fully efficacious in estrogen receptor α, β knock-out mice. Finally, we observed that the putative membrane-associated estrogen receptor is different from GPR30 in arcuate neurons using whole-cell patch recording in hypothalamic slices from GPR30 knock-out mice. Collectively, these findings suggest that the mER is distinct from ERα, ERβ or GPR30.

Original languageEnglish (US)
Pages (from-to)985-991
Number of pages7
JournalSteroids
Volume73
Issue number9-10
DOIs
StatePublished - Oct 1 2008

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Keywords

  • G-protein-coupled receptor
  • GABA receptor
  • GPR30
  • POMC neurons
  • Potassium channels

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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