Involvement of G protein-coupled receptor 30 (GPR30) in rapid action of estrogen in primate LHRH neurons

Mol Endocrinol. 2009 Mar;23(3):349-59. doi: 10.1210/me.2008-0299. Epub 2009 Jan 8.


Previously, we have reported that 17beta-estradiol (E(2)) induces an increase in firing activity of primate LH-releasing hormone (LHRH) neurons. The present study investigates whether E(2) alters LHRH release as well as the pattern of intracellular calcium ([Ca(2+)](i)) oscillations and whether G protein-coupled receptor 30 (GPR30) plays a role in mediating the rapid E(2) action in primate LHRH neurons. Results are summarized: 1) E(2), the nuclear membrane-impermeable estrogen, estrogen-dendrimer conjugate, and the plasma membrane-impermeable estrogen, E(2)-BSA conjugate, all stimulated LHRH release within 10 min of exposure; 2) whereas the estrogen receptor antagonist, ICI 182,780, did not block the E(2)-induced LHRH release, E(2) application to cells treated with pertussis toxin failed to induce LHRH release; 3) GPR30 mRNA was expressed in olfactory placode cultures, and GPR30 protein was expressed in a subset of LHRH neurons; 4) pertussis toxin treatment blocked the E(2)-induced increase in [Ca(2+)](i) oscillations; 5) knockdown of GPR30 in primate LHRH neurons by transfection with small interfering RNA (siRNA) for GPR30 completely abrogated the E(2)-induced changes in [Ca(2+)](i) oscillations, whereas transfection with control siRNA did not; 6) the estrogen-dendrimer conjugate-induced increase in [Ca(2+)](i) oscillations also did not occur in LHRH neurons transfected with GPR30 siRNA; and 7) G1, a GPR30 agonist, resulted in changes in [Ca(2+)](i) oscillations, similar to those observed with E(2). Collectively, E(2) induces a rapid excitatory effect on primate LHRH neurons, and this rapid action of E(2) appears to be mediated, in part, through GPR30.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium Signaling / drug effects
  • Cells, Cultured
  • Dendrimers / pharmacology
  • Embryo, Mammalian
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology*
  • Estrogens, Conjugated (USP) / pharmacology
  • Female
  • Fulvestrant
  • Gonadotropin-Releasing Hormone / metabolism*
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Macaca mulatta
  • Neurons / drug effects*
  • Neurons / metabolism
  • Olfactory Pathways / drug effects
  • Olfactory Pathways / metabolism
  • Pertussis Toxin / pharmacology
  • Pregnancy
  • Primates* / metabolism
  • Primates* / physiology
  • RNA, Small Interfering / pharmacology
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology*
  • Serum Albumin, Bovine / pharmacology
  • Synaptic Transmission / drug effects


  • Dendrimers
  • Estrogens, Conjugated (USP)
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • estradiol-bovine serum albumin
  • Fulvestrant
  • Serum Albumin, Bovine
  • Gonadotropin-Releasing Hormone
  • Estradiol
  • Pertussis Toxin