Dopaminergic Mechanisms Involved in Prolactin Release after Mifepristone and Naloxone Treatment during Late Pregnancy in the Rat

SOAJE M; VALDEZ S; BREGONZIO C; PENISSI A; DEIS RP

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2006 vol. 84 p. 58 - 67

0028-3835

AbstractBackground/Aims: During late pregnancy, the antiprogesteronemifepristone facilitates prolactin release. This effectis enhanced by administration of the opioid antagonist naloxone,suggesting an inhibitory-neuromodulatory role ofthe opioid system. Since hypothalamic dopamine (DA) is themain regulator of prolactin release, in this study we exploredthe role of DA on prolactin release induced by mifepristoneand naloxone treatment. Methods/Results: Rats on day 19of pregnancy were used. Naloxone treatment did not modifythe 3,4-dihydroxyphenylacetic acid/DA (DOPAC/DA) ratioor serum prolactin concentration in control rats. After mifepristonetreatment, DA activity diminished significantlywithout modifying serum prolactin levels. Naloxone administrationto antiprogesterone-treated rats did not changethe DOPAC/DA ratio but increased serum prolactin. Tyrosinehydroxylase (TH) expression in medial basal hypothalamus(MBH) protein extracts was lowered by pretreatment withmifepristone, with no additional effect of naloxone. Whilemifepristone decreased the intensity of TH immunoreactivityin the arcuate and periventricular nuclei and in fibers ofthe median eminence, naloxone treatment had no further effect.Conclusions: (1) A reduction of tubero infundibular dopaminergic(TIDA) neuron activity is suggested by the fall ofthe DOPAC/DA ratio and the low expression of MBH TH;(2) this reduction facilitates prolactin secretion by naloxone,indicating that progesterone stimulates DA neurons tomaintain low serum prolactin; (3) naloxone action seems todepend on a previous decrease of DA tone induced by mifepristone,without involve a direct effect on neuronal DA activity,and (4) endogenous opioids may inhibit prolactin secretionthrough a non-dopaminergic neuronal system thatregulates prolactin secretion in which as yet undeterminedprolactin-releasing factors may participate.