A MODULATORY ROLE OF ENDOGENOUS OPIOIDS ON PROLACTIN SECRETION AT THEEND OF PREGNANCY IN THE RAT

It is well known that the fall in serum progesterone concentrations du ring late pregnancy induces prolactin secretion in rats. On day 19 of pregnancy, administration of 10 mg of the antiprogesterone RU-486/kg i nduced a small but significant increase in serum prolactin. A lower do se (2mg/kg) was not effective. Administration of naloxone (2 mg/kg) to pregnant rats on day 19 of pregnancy did not modify circulating prola ctin but, after RU-486 treatment, a notable increase in serum prolacti n was obtained 30 min after naloxone was given. The lack of effect of naloxone-methobromide in pregnant rats pretreated with RU-486 may indi cate that the opioid-induced prolactin suppression acts centrally, mos t probably at the hypothalamic level. During day 21 of pregnancy, the time-course of prolactin secretion, measured at 0900, 1400, 1900 and 2 200 h, was inversely correlated with circulating progesterone levels. At 0900 h, serum prolactin was very low with high serum progesterone c oncentrations but a significant increase in serum prolactin occurred a t 2200 h; this was coincident with a significant decrease in the stero id. The stimulatory effect of naloxone on prolactin secretion was clea rly dependent on the circulating progesterone level. Thus, at 1900 h o f day 21, naloxone induced a significant increase in serum prolactin b ut, at 2200 h, the opioid antagonist dramatically enhanced the circula ting level of prolactin. The serum prolactin increase induced by nalox one at 1900 h was prevented by the s.c. administration of 5 mg progest erone given 7h earlier. Similarly, the large increase in serum prolact in levels at 1800 h on day 19 of pregnancy, after administration of RU -486 plus naloxone, was completely abolished by treatment with CB154. The lack of effect of RU-486 and naloxone on serum prolactin levels in virgin rats on the day of pro-oestrus demonstrates that the effect of naloxone on prolactin in pregnant rat is peculiar to the end of pregn ancy. In conclusion, the attenuation of the central inhibitory action of progesterone facilitates the release of prolactin which is dramatic ally enhanced by naloxone treatment. These results provide an importan t new insight into the existence of a neuromodulatory regulation of pr olactin secretion by the opioid system showing a paradoxical opioid-in duced prolactin suppression at the end of pregnancy.