Prolactin-sensitive neurons express estrogen receptor-alpha and depend on sex hormones for normal responsiveness to prolactin

Autor(es)

Furigo, Isadora C. ^[1] ; Kim, Ki Woo ^{[2, 3]} ; Nagaishi, Vanessa S. ^[1] ; Ramos-Lobo, Angela M. ^[1] ; de Alencar, Amanda ^[1] ; Pedroso, Joao A. B. ^[1] ; Metzger, Martin ^[1] ; Donato, Jr., Jose ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Yonsei Univ, Wonju Coll Med, Inst Lifestyle Med, Dept Pharmacol, Wonju 220701 - South Korea

^[3] Yonsei Univ, Wonju Coll Med, Nucl Receptor Res Consortium, Wonju 220701 - South Korea

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1566, p. 47-59, MAY 30 2014.
• Citações Web of Science: 23

Resumo

Estrogens and prolactin share important target tissues, including the gonads, brain, liver, kidneys and some types of cancer cells. Herein, we sought anatomical and functional evidence of possible crosstalk between prolactin and estrogens in the mouse brain. First, we determined the distribution of prolactin-responsive neurons that express the estrogen receptor alpha (ER alpha). A large number of prolactin-induced pSTAT5-immunoreactive neurons expressing ERa mRNA were observed in several brain areas, including the anteroventral periventricular nucleus, medial preoptic nucleus, arcuate nucleus of the hypothalamus, ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMH), medial nucleus of the amygdala and nucleus of the solitary tract. However, although the medial preoptic area, periventricular nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus, retrochiasmatic area, dorsomedial subdivision of the VMH, lateral hypothalamic area, dorsomedial nucleus of the hypothalamus and ventral premammillary nucleus contained significant numbers of prolactin-responsive neurons, these areas showed very few pSTAT5-immunoreactive cells expressing ER alpha mRNA. Second, we evaluated prolactin sensitivity in ovariectomized mice and observed that sex hormones are required for a normal responsiveness to prolactin as ovariectomized mice showed a lower number of prolactin-induced pSTAT5 immunoreactive neurons in all analyzed brain nuclei compared to gonad-intact females. In addition, we performed hypothalamic gene expression analyses to determine possible post-ovariectomy changes in components of prolactin signaling. We observed no significant changes in the mRNA expression of prolactin receptor, STAT5a or STAT5b. In summary, sex hormones exert a permissive role in maintaining the brain's prolactin sensitivity, most likely through post-transcriptional mechanisms. (C) 2014 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 13/21722-4 - Estudo do mecanismo de ação da Bromocriptina e de antagonistas de prolactina no tratamento do Diabetes Mellitus tipo 2 e da Obesidade.
• Beneficiário: Isadora Clivatti Furigo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/02388-3 - Topografia e assinatura neuroquímica das projeções entre a habenula lateral, o núcleo rostromedial tegmental e o núcleo dorsal da rafe no rato
• Beneficiário: Martin Andreas Metzger
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/18086-0 - Bases moleculares da resistência à leptina
• Beneficiário: Jose Donato Junior
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/16374-7 - Interação entre leptina e prolactina no encéfalo: possível mecanismo de alterações metabólicas na gravidez
• Beneficiário: Vanessa Sayuri Nagaishi
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica