A modulatory role of endogenous opioids on prolactin secretion at the end of pregnancy in the rat

SOAJE M; DEIS RP

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 1994 vol. 140 p. 97 - 102

0022-0795

It is well known that the fall in serum progesteroneconcentrations during late pregnancy induces prolactinsecretion in rats. On day 19 of pregnancy, administrationof 10 mg of the antiprogesterone RU-486/kg induced asmall but significant increase in serum prolactin. A lowerdose (2 mg/kg) was not effective. Administration ofnaloxone (2 mg/kg) to pregnant rats on day 19 of pregnancydid not modify circulating prolactin but, afterRU-486 treatment, a notable increase in serum prolactinwas obtained 30 min after naloxone was given. The lackof effect of naloxone-methobromide in pregnant ratspretreated with RU-486 may indicate that the opioid\x=req-\induced prolactin suppression acts centrally, mostprobably at the hypothalamic level. During day 21 ofpregnancy, the time-course of prolactin secretion,measured at 0900, 1400, 1900 and 2200 h, was inverselycorrelated with circulating progesterone levels. At 0900 h,serum prolactin was very low with high serum progesteroneconcentrations but a significant increase in serumprolactin occurred at 2200 h; this was coincident with asignificant decrease in the steroid. The stimulatory effectof naloxone on prolactin secretion was clearly dependenton the circulating progesterone level. Thus, at 1900 h ofday 21, naloxone induced a significant increase in serumprolactin but, at 2200 h, the opioid antagonist dramaticallyenhanced the circulating level of prolactin. The serumprolactin increase induced by naloxone at 1900 h wasprevented by the s.c. administration of 5 mg progesteronegiven 7 h earlier. Similarly, the large increase in serumprolactin levels at 1800 h on day 19 of pregnancy, afteradministration of RU-486 plus naloxone, was completelyabolished by treatment with CB154. The lack of effect ofRU-486 and naloxone on serum prolactin levels in virginrats on the day of pro-oestrus demonstrates that the effectof naloxone on prolactin in pregnant rat is peculiar to theend of pregnancy.In conclusion, the attenuation of the central inhibitoryaction of progesterone facilitates the release of prolactinwhich is dramatically enhanced by naloxone treatment.These results provide an important new insight into theexistence of a neuromodulatory regulation of prolactinsecretion by the opioid system showing a paradoxicalopioid-induced prolactin suppression at the end ofpregnancy.