Estradiol-17β and μ-opioid peptides rapidly hyperpolarize GnRH neurons: A cellular mechanism of negative feedback?

Andre H. Lagrange, Oline Ronnekleiv, Martin Kelly

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Control of the HPG axis involves a rapid (30 min) inhibition of LH (GnRH) release by E2. The time course of this effect is faster than expected for a purely transcriptional mechanism of E2 action. To elucidate the mechanism of E2 action, intracellular recordings in TTX were performed in guinea pig hypothalamic GnRH neurons. These neurons were directly hyperpolarized by both the μ-opioid agonist, DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol, 9 mV) and the GABA(B) agonist, baclofen (18 mV) by opening K+ channels. Schild analysis with naloxone (K(e) = 2.4 nM) confirmed that μ-opioid receptors mediated the effect of DAMGO. E2 also directly hyperpolarized GnRH neurons by opening K+ channels. Coupled with previous work showing a rapid effect of E2 to alter μ-opioid potency (1), a model is presented in which E2 rapidly inhibits GnRH neurons through parallel, possibly synergistic pathways.

Original languageEnglish (US)
Pages (from-to)2341-2344
Number of pages4
JournalEndocrinology
Volume136
Issue number5
DOIs
StatePublished - 1995

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Opioid Peptides
Gonadotropin-Releasing Hormone
Estradiol
alanylglycine
Neurons
Opioid Analgesics
GABA-B Receptor Agonists
Baclofen
Opioid Receptors
Naloxone
Guinea Pigs

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Estradiol-17β and μ-opioid peptides rapidly hyperpolarize GnRH neurons : A cellular mechanism of negative feedback? / Lagrange, Andre H.; Ronnekleiv, Oline; Kelly, Martin.

In: Endocrinology, Vol. 136, No. 5, 1995, p. 2341-2344.

Research output: Contribution to journalArticle

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