Effect of progesterone on the activation of neurones of the supraoptic nucleus during parturition

Parturition is driven by a pulsatile pattern of oxytocin secretion, resulti ng from burst firing activity of supraoptic oxytocin neurones and reflected by induction of Fos expression. Rats were injected with progesterone on da y 20 of pregnancy to investigate the role of the decreasing progesterone:oe strogen ratio, which precedes delivery, in the activation of supraoptic neu rones. Progesterone delayed the onset of birth by 28 h compared with vehicl e (control) and prolonged the duration of delivery, which was overcome by p ulsatile injections of oxytocin, indicating that the slow delivery may refl ect impaired oxytocin secretion. Parturient rats pretreated with progestero ne had fewer Fos immunoreactive nuclei in the supraoptic nucleus than did p arturient rats pretreated with vehicle. The number of Fos immunoreactive nu clei was not restored after oxytocin injection, indicating that appropriate activation of oxytocin neurones is impaired by progesterone and also that there is a lack of stimulatory afferent drive. Fos expression increased in the nucleus of the tractus solitarius during parturition in rats pretreated with either vehicle or progesterone, but not in rats that had been pretrea ted with progesterone and induced with oxytocin, indicating that this input was inhibited. Endogenous opioids inhibit oxytocin neurones in late pregna ncy and the opioid antagonist, naloxone, increases Fos expression in suprao ptic nuclei by preventing inhibition. However, progesterone attenuated nalo xone-induced Fos expression in the supraoptic nucleus in late pregnancy and naloxone administered during parturition did not accelerate the duration o f births delayed by progesterone administration, indicating that progestero ne does not act by hyperactivation of endogenous opioid tone. RU486, a prog esterone receptor antagonist, enhanced supraoptic neurone Fos expression in late pregnancy, indicating progesterone receptor-mediated actions. Thus, p rogesterone withdrawal is necessary for appropriate activation of supraopti c and tractus solitarius neurones during parturition.