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Pathways to parturition

A J Douglas1, R J Bicknell, J A Russell

  • 1Department of Physiology, University Medical School, Edinburgh, Scotland, United Kingdom.

Advances in Experimental Medicine and Biology
|January 1, 1995
PubMed
Summary

Endogenous opioids inhibit oxytocin secretion during late pregnancy. Naloxone, an opioid antagonist, removes this inhibition, activating oxytocin neurons via mu-opioid receptors, suggesting pre-synaptic action.

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Area of Science:

  • Neuroendocrinology
  • Reproductive Physiology

Background:

  • Oxytocin is crucial for myometrial contractions and birth during parturition.
  • Oxytocin neurons undergo preparation for labor, with secretion limited by endogenous opioid inhibition in late pregnancy.

Purpose of the Study:

  • To investigate the mechanism of opioid inhibition on oxytocin secretion during late pregnancy.
  • To determine the specific opioid receptors and locations involved in this inhibitory pathway.

Main Methods:

  • Administration of opioid antagonist naloxone and kappa-opioid agonist U50,488.
  • Measurement of kappa-receptor binding and Fos protein expression in the supraoptic nucleus.
  • Assessment of oxytocin neuron firing rate response to cholecystokinin.
  • Measurement of beta-endorphin, proopiomelanocortin (POMC) mRNA, prodynorphin, and proenkephalin A levels.

Main Results:

  • Opioid inhibition of oxytocin secretion is limited in late pregnancy, with desensitization at nerve terminals.
  • Naloxone activates oxytocin cell bodies via mu-opioid receptors, not kappa-opioid receptors.
  • Endogenous opioids likely act pre-synaptically on inputs to oxytocin neurons, potentiated by naloxone.
  • Beta-endorphin may be the primary endogenous opioid responsible for inhibition, indicated by increased peptide and POMC mRNA in the arcuate nucleus.

Conclusions:

  • Opioid inhibition of oxytocin neurons is mediated pre-synaptically via mu-opioid receptors during late pregnancy.
  • Beta-endorphin is a likely candidate for this inhibitory role.
  • Understanding these mechanisms is vital for managing labor and postpartum complications.

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