Dopaminergic mechanisms involved in prolactin release after mifepristone and naloxone treatment during late pregnancy in the rat.
OBJECTIVE
During late pregnancy, the antiprogesterone mifepristone facilitates prolactin release. This effect is enhanced by administration of the opioid antagonist naloxone, suggesting an inhibitory-neuromodulatory role of the opioid system. Since hypothalamic dopamine (DA) is the main regulator of prolactin release, in this study we explored the role of DA on prolactin release induced by mifepristone and naloxone treatment.


RESULTS
Rats on day 19 of pregnancy were used. Naloxone treatment did not modify the 3,4-dihydroxyphenylacetic acid/DA (DOPAC/DA) ratio or serum prolactin concentration in control rats. After mifepristone treatment, DA activity diminished significantly without modifying serum prolactin levels. Naloxone administration to antiprogesterone-treated rats did not change the DOPAC/DA ratio but increased serum prolactin. Tyrosine hydroxylase (TH) expression in medial basal hypothalamus (MBH) protein extracts was lowered by pretreatment with mifepristone, with no additional effect of naloxone. While mifepristone decreased the intensity of TH immunoreactivity in the arcuate and periventricular nuclei and in fibers of the median eminence, naloxone treatment had no further effect.


CONCLUSIONS
(1) A reduction of tuberoinfundibular dopaminergic (TIDA) neuron activity is suggested by the fall of the DOPAC/DA ratio and the low expression of MBH TH; (2) this reduction facilitates prolactin secretion by naloxone, indicating that progesterone stimulates DA neurons to maintain low serum prolactin; (3) naloxone action seems to depend 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 secretion through a non-dopaminergic neuronal system that regulates prolactin secretion in which as yet undetermined prolactin-releasing factors may participate.
Soaje
Marta
M
Laboratorio de Reproducción y Lactancia, IMBECU-CONICET, Mendoza, Argentina. msoaje@lab.cricyt.edu.ar
Valdez
Susana
S
Bregonzio
Claudia
C
Penissi
Alicia
A
Deis
Ricardo P
RP
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000235:genetics / Q000378:metabolism*; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D006834:Hydrazines; D009292:Narcotic Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D015735:Mifepristone; D009270:Naloxone; D011388:Prolactin; C004297:3-hydroxybenzylhydrazine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine