The Maintenance of Normal Parturition in the Rat Requires Neurohypophysial Oxytocin

Abstract

The neuropeptide oxytocin has long been known as a potent contractor of the uterus. However, it has remained difficult to attribute a definite role for neurohypophysial oxytocin in either the initiation or continuation of labour. Most recently, Lefebvre and colleagues have suggested that oxytocin produced in the uterus, rather than in the hypothalamus, may be more important in parturition since at term the uterus of the rat contains 70-fold more mRNA for oxytocin than the hypothalamus, and this disappears at about the time of parturition. Despite the high levels of mRNA the uterus contains only nanogram quantities of immunoreactive oxytocin per gram wet weight at term, compared to microgram quantities present in the pituitary. Here we show that activation of the neurohypophysial oxytocin system occurs, as reflected by expression of immunoreactivity for Fos in the hypothalamic supraoptic nucleus, and that this activation is indeed critical for normal parturition, since its inhibition results in a significant prolongation of parturition. In addition, we present evidence that pulsatile delivery of oxytocin into the circulation is important for the efficient progress of parturition, indicating that a major role of the neuronal circuits regulating oxytocin secretion for parturition, as is already known for suckling, is to produce an appropriately patterned hormonal output for efficient biological action.

Sex, parturition and motherhood without oxytocin?

“…Pulsatile i.v. injection of oxytocin (OXT 1 mU (2 ng; 2 pmoles) every 10 min) after a single injection of morphine after the birth of pup 2 fully restored the progress of normal parturition; continuous infusion (not shown) of the same total dose of oxytocin was ineffective (data from Luckman et al 1993, Antonijevic et al 1995a. The prolonged inhibitory action of the oxytocin antagonist clearly indicates an important role for oxytocin in promoting parturition.…”

“…The pulsatile secretion derives from the synchronised intense bursting activity of oxytocin neurones in the hypothalamus in the rat and rabbit (Summerlee 1981, O'Byrne et al 1986, activity similar to that in the rat during reflex milk ejection in response to suckling. The increased electrical activity is accompanied by induction in these neurones of the immediate-early gene c-fos, an indicator of trans-synaptic activation of the neurones, and consequent prominent expression of the protein product Fos in the nuclei of oxytocin cells (Luckman et al 1993). Furthermore, expression of the oxytocin gene in supraoptic neurones is stimulated at parturition (Douglas et al 1998), while it is controversial whether expression is increased in pregnancy (Horwitz et al 1994, Douglas et al 1998.…”

“…The secreted oxytocin enters the circulation at a time when uterine responsiveness to oxytocin is maximal as a result of a rapid increase in oxytocin receptor expression in the myometrium at the end of pregnancy (Rozen et al 1995). Inhibition of oxytocin secretion by exogenous opiates (which act to inhibit the oxytocin neurones directly) slows down the early progress of parturition, and this can be reversed by oxytocin infusion (Russell et al 1989), with pulsatile delivery of oxytocin being particularly effective (Luckman et al 1993, Antonijevic et al 1995b (Fig. 2).…”

“…The prolonged inhibitory action of the oxytocin antagonist clearly indicates an important role for oxytocin in promoting parturition. The inhibitory effects of morphine are a consequence of inhibition of the secretion of oxytocin from the posterior pituitary gland: morphine inhibits the firing of magnocellular oxytocin neurones via µ-opioid receptors on their cell bodies or inputs, and like other opiates it decreases oxytocin secretion in parturition (Russell et al 1989, Douglas et al 1993. The restoration of the normal progress of parturition by i.v.…”

The effect of opioid antagonism and environmental restriction on plasma oxytocin and vasopressin concentrations in parturient gilts

“…Pulsatile neurohypophysial oxytocin release is required for the maintenance of normal parturition (Luckman et al 1993), and inhibition of oxytocin release by antagonists has been shown to prolong the expulsive phase in rats (Antonijevic et al 1995) and guinea pigs (Schellenberg 1995). In the pig, prolonged parturition is associated with low basal and peak levels of oxytocin during the expulsive phase (Castren et al 1993).…”