Sex-steroid induction of endogenous opioid inhibition on oxytocin secretory responses to stress

In pregnancy, endogenous opioids inhibit enhanced basal and stressor-stimul ated oxytocin neurone activity and secretion. By contrast, stress responses of the hypothalamo-pituitary-adrenal (HPA) axis are reduced in pregnancy. We investigated whether the high levels of oestradiol and progesterone of p regnancy could induce these changes. Silastic capsules containing oestradio l or progesterone (or control capsules) were implanted s.c. in virgin femal e rats for 16 or 17 days, with or without progesterone removal on day 15 to mimic the progesterone withdrawal seen at the end of pregnancy. Plasma con centrations of oxytocin, adrenocorticotrophic hormone (ACTH) and corticoste rone were measured in jugular vein blood samples from conscious rats. Under basal conditions, naloxone (5 mg/kg) increased oxytocin secretion in all g roups, but had no greater effect in sex-steroid treated rats, and did not i nduce Fos expression in the supraoptic nucleus. Forced swimming, a stressor , increased oxytocin secretion at 5 min in vehicle-injected controls, and t his response was slightly attenuated in the sex-steroid treated groups. Pre treatment with naloxone greatly enhanced the response in the sex-steroid tr eated rats, and was less effective in the controls. in rats treated with oe stradiol alone, naloxone prolonged the response. Thus, the combined sex-ste roid treatment enhanced the responsiveness of oxytocin neurones to the stre ssor, while simultaneously restraining oxytocin secretion via endogenous op ioid inhibition. In the same rats, ACTH and corticosterone secretion was al so stimulated by the stressor, but the hypothalamopituitary-adrenal (HPA) a xis response was not attenuated in sex-steroid treated rats. Naloxone weakl y reduced the HPA axis response in controls and was ineffective in the sex- steroid treated rats. We conclude that oestradiol and progesterone may be r esponsible for inducing the opioid restraint and enhanced oxytocin neurone responsiveness in pregnancy.