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

Isadora C. Furigo, Ki Woo Kim, Vanessa S. Nagaishi, Angela M. Ramos-Lobo, Amanda De Alencar, João A.B. Pedroso, Martin Metzger, Jose Donato

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42 Citations (Scopus)


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 α (ERα). A large number of prolactin-induced pSTAT5-immunoreactive neurons expressing ERα 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 ERα 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 brains prolactin sensitivity, most likely through post-transcriptional mechanisms.

Original languageEnglish
Pages (from-to)47-59
Number of pages13
JournalBrain Research
Publication statusPublished - 2014 May 30

Bibliographical note

Funding Information:
We thank the São Paulo Research Foundation (FAPESP-Brazil, 2010/18086-0 , 2012/02388-3 , 2013/16374-7 and 2013/21722-4 ) and the International Brain Research Organization (IBRO) for their financial support and fellowships, and Ana Maria P. Campos and José L. dos Santos for the technical assistance. This research was also partly supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning ( NRF-2013R1A1A1007693 to K.W.K).

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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