Estradiol-17 beta and mu-opioid peptides rapidly hyperpolarize GnRH neurons: a cellular mechanism of negative feedback?

Lagrange AH, R√łnnekleiv OK, Kelly MJ
Endocrinology. 1995 136 (5): 2341-4

PMID: 7720682 · DOI:10.1210/endo.136.5.7720682

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 mu-opioid agonist, DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol, 9 mV) and the GABAB agonist, baclofen (18 mV) by opening K+ channels. Schild analysis with naloxone (Ke = 2.4 nM) confirmed that mu-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 mu-opioid potency (1), a model is presented in which E2 rapidly inhibits GnRH neurons through parallel, possibly synergistic pathways.

MeSH Terms (18)

Animals Arcuate Nucleus of Hypothalamus Baclofen Drug Interactions Enkephalin, Ala(2)-MePhe(4)-Gly(5)- Enkephalins Estradiol Feedback Female Gonadotropin-Releasing Hormone Guinea Pigs Membrane Potentials Naloxone Neurons Ovariectomy Potassium Channels Receptors, Opioid, mu Tetrodotoxin

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