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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Brain Research; v. 1566, p. 47-59, MAY 30 2014.
• Web of Science Citations: 23

Abstract

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)

• FAPESP's process: 13/21722-4 - Mechanism of action of bromocriptine and prolactin antagonists in the treatment of Diabetes and Obesity
• Grantee: Isadora Clivatti Furigo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/02388-3 - Topography and transmitter phenotype of the projections between the lateral habenula, the rostromedial tegmental nucleus and the dorsal raphe nucleus in the rat
• Grantee: Martin Andreas Metzger
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/18086-0 - Molecular basis of leptin resistance
• Grantee: Jose Donato Junior
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/16374-7 - Crosstalk between leptin and prolactin in the brain: possible mechanism of metabolic changes during pregnancy
• Grantee: Vanessa Sayuri Nagaishi
• Support Opportunities: Scholarships in Brazil - Scientific Initiation