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

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Abstract

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 (ERα and β, PRs, PRLR(long)), and μ- and κ- opioid receptors (ORs) at mRNA (by semiquantitative RT-PCR) and protein (by western blot for TH, PRLR(long), ERα, PRs, μ- and ORs) levels in extracts of medial basal hypothalamus (MBH) and serum PRL, E2 and P4 levels (by RIA) in mifepristone- and naloxone-treated rats. Tamoxifen administration partially prevented PRL release induced by the combined treatment. TH expression diminished and ERα 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 μ- and k-ORs mRNA but not protein levels. In conclusion, E2 induces neuroadaptive mechanisms necessary to facilitate PRL release preceding delivery. Acting through ERα, E2 modulates hypothalamic dopaminergic neurons activity, regulating TH, μ- and κ-ORs and PRLR(long) expression, and is necessary for evidencing the effects of P4 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.

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Acknowledgments

The authors are grateful to Mr. J. Rosales for his skilful technical assistance.

Funding

This work has been supported by PIP 2012–2014 00863-CONICET (Consejo Nacional de Investigaciones Científicas y Tecnológicas) and Proyecto 06/J458, SeCTyP, Universidad Nacional de Cuyo. CVG, GEP, GAJ and MS are members of CONICET.

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  1. Laboratorio de Reproducción y Lactancia, IMBECU-CONICET, Casilla de Correo 855, 5500, Mendoza, Argentina

    Carlos Villegas-Gabutti, Gisela E. Pennacchio, Graciela A. Jahn & Marta Soaje

  2. Facultad de Ciencias Médicas, Instituto de Fisiología, Universidad Nacional de Cuyo, Mendoza, Argentina

    Marta Soaje

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  1. Carlos Villegas-Gabutti
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  2. Gisela E. Pennacchio
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  3. Graciela A. Jahn
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  4. Marta Soaje
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Correspondence to Marta Soaje.

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Villegas-Gabutti, C., Pennacchio, G.E., Jahn, G.A. et al. Role of Estradiol in the Regulation of Prolactin Secretion During Late Pregnancy. Neurochem Res 41, 3344–3355 (2016). https://doi.org/10.1007/s11064-016-2067-x

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