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

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90 Citations (Scopus)

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 2008

Fingerprint

GTP-Binding Proteins
Estrogen Receptors
Estrogens
Modulation
Neurons
Membranes
Knockout Mice
Guinea Pigs
Pro-Opiomelanocortin
Type C Phospholipases
Patch-Clamp Techniques
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Energy Metabolism
Reproduction
Estradiol
Brain
Sleep
Chemical activation
Temperature

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

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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.",
keywords = "G-protein-coupled receptor, GABA receptor, GPR30, POMC neurons, Potassium channels",
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