Role of Estradiol in the Regulation of Prolactin Secretion During Late Pregnancy

Estrogen action is necessary for evidencing the stimulatory action of mifepristone and naloxone on prolactin (PRL) secretion during late pregnancy. Our aim is to determine the mechanism mediating this facilitator action of estrogens. To investigate the hypothalamic mechanisms involved in estrogen actions in PRL secretion at the end of pregnancy, we measured the effect of pretreatment with the estrogen antagonist tamoxifen on the expression of tyrosine hydroxylase (TH), hormone receptors (ER alpha and beta, PRs, PRLR(long)), and mu- and kappa- opioid receptors (ORs) at mRNA (by semiquantitative RT-PCR) and protein (by western blot for TH, PRLR(long), ER alpha, PRs, mu- and ORs) levels in extracts of medial basal hypothalamus (MBH) and serum PRL, E-2 and P-4 levels (by RIA) in mifepristone- and naloxone-treated rats. Tamoxifen administration partially prevented PRL release induced by the combined treatment. TH expression diminished and ER alpha expression increased in mifepristone-treated rats at mRNA and protein levels and tamoxifen partially prevented these changes with no effect on PRs expression. Mifepristone increased PRLR(long) mRNA levels; this increase was blocked by tamoxifen. Combined tamoxifen and mifepristone treatment decreased mu- and k-ORs mRNA but not protein levels. In conclusion, E-2 induces neuroadaptive mechanisms necessary to facilitate PRL release preceding delivery. Acting through ER alpha, E-2 modulates hypothalamic dopaminergic neurons activity, regulating TH, mu- and kappa-ORs and PRLR(long) expression, and is necessary for evidencing the effects of P-4 withdrawal. Its presence on days 14 and 15 of pregnancy is crucial to facilitate the opioid system modulation of PRL secretion at the end of pregnancy in the rat.