Endogenous opioid regulation of oxytocin and ACTH secretion during pregnancy and parturition.

Progress of parturition in the rat is optimal when there is increased oxytocin secretion, thus ensuring quick birth and otherwise risking adverse neonatal health. To ensure that the mechanisms for this are available, oxytocin neurons adapt in pregnancy and this includes development of a tonic inhibition by endogenous opioids. Endogenous opioid inhibition of oxytocin secretion increases in pregnancy, initially acting on the nerve terminals in the posterior pituitary and later on oxytocin cell bodies and their inputs. This inhibition enhances stores of oxytocin and enables restraint of oxytocin neuron responsiveness to selected excitatory inputs. The hypothalamic neurons which mediate stress also adapt in late pregnancy so that hypothalamo-pituitary-adrenal axis and oxytocin secretory responses to stressor exposure are attenuated. This is also partly due to endogenous opioid inhibition. Thus, in pregnancy oxytocin and hypothalamo-pituitary-adrenal axis secretion in response to stimulation is restrained, protecting the unborn fetus(es) from premature delivery and glucocorticoid exposure and preparing the oxytocin neurons for their important secretory role during parturition. In parturition itself, endogenous opioids continue to inhibit these neurons. Stress exposure during parturition delays births, probably due to endogenous opioid inhibition of pulsatile oxytocin secretion. On the other hand, basal ACTH and corticosterone secretion are reduced in parturition through inhibition by endogenous opioids. So, opioids continue to regulate the activity of oxytocin and hypothalamo-pituitary-adrenal mechanisms in labor; inhibition of oxytocin neurons at this time may control the spacing of pup births.