OPIOIDERGIC REGULATION OF PROLACTIN SECRETION DURING PREGNANCY - ROLEOF OVARIAN HORMONES

We have recently demonstrated the existence of a neuromodulatory regul ation of prolactin secretion by the opioid system showing a paradoxica l opioid-induced prolactin suppression at the end of pregnancy. The ai m of this study was to determine a possible interaction between the op ioid system and ovarian hormones on the release of prolactin during pr egnancy. Serum prolactin levels measured at 1800 h were significantly higher on days 3 and 6 of pregnancy when compared with the other days of gestation. These increases in serum prolactin were reduced signific antly by naloxone (2mg/kg) administered at 1730h and by RU-486 (10 mg/ kg) administered at 0800 h. The response induced by RU-486 was potenti ated by naloxone only on day 3. On days 7, 13 and 16, prolactin secret ion was not modified by RU-486 and/or naloxone treatment. In RU-486 pr etreated rats, naloxone administration increased serum prolactin level s only on day 16 of pregnancy. Interestingly, progesterone treatment ( 0.5 mg/rat) on days 13, 14 and 15 of pregnancy prevented the high incr ease in serum prolactin induced by RU-486 and naloxone on day 16 of pr egnancy. The progressive increase and decrease of serum progesterone c oncentration during pregnancy was not modified by naloxone treatment. The participation of oestrogen in the regulation of prolactin secretio n by the opioid system on days 3, 16 and 19 was examined by treating t hese groups of rats with oestradiol benzoate or tamoxifen citrate. Oes tradiol (2 mu g/rat) significantly increased serum prolactin levels on day 3 and naloxone administration did not modify this increase. No ef fect was observed after oestradiol (5 mu g/rat) and naloxone treatment on days 16 and 19 of pregnancy. Oral administration of tamoxifen (500 mu g/kg) the previous day did not modify the serum prolactin concentr ation measured at 1800 h in oil-treated rats on days 3, 16 and 19 of p regnancy. The antioestrogen completely abolished the naloxone-induced prolactin secretion on day 16 in rats pretreated with RU-486 but no ef fect was observed on day 19. When tamoxifen was administered on days 1 4 and 15 of pregnancy, the high serum prolactin levels on day 19 induc ed by treatment with RU-486 and naloxone were significantly reduced. I n conclusion, these results provide an important new insight into the existence of a dual neuromodulatory regulation of prolactin secretion by the opioid system during pregnancy. After a stimulatory action duri ng the first days, there is a change to an inhibitory control at the e nd of pregnancy, starting around day 16. Moreover, the activation of t he inhibitory modulation of the opioid system on prolactin secretion o n days 16 and 19 of pregnancy seems to be mediated by changes in the o estrogen and progesterone action.