Furigo Isadora C, Kim Ki Woo, Nagaishi Vanessa S, Ramos-Lobo Angela M, de Alencar Amanda, Pedroso João A B, Metzger Martin, Donato Jose
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Department of Pharmacology, Institute of Lifestyle Medicine, and Nuclear Receptor Research Consortium, Yonsei University Wonju College of Medicine, Wonju 220-701, Republic of Korea.
Brain Res. 2014 May 30;1566:47-59. doi: 10.1016/j.brainres.2014.04.018. Epub 2014 Apr 19.
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 brain's prolactin sensitivity, most likely through post-transcriptional mechanisms.
雌激素和催乳素拥有重要的共同靶组织,包括性腺、脑、肝脏、肾脏以及某些类型的癌细胞。在此,我们探寻了小鼠脑中催乳素与雌激素之间可能存在的相互作用的解剖学和功能证据。首先,我们确定了表达雌激素受体α(ERα)的催乳素反应性神经元的分布。在几个脑区观察到大量催乳素诱导的pSTAT5免疫反应性神经元表达ERα mRNA,这些脑区包括室旁前腹核、视前内侧核、下丘脑弓状核、下丘脑腹内侧核腹外侧亚区(VMH)、杏仁核内侧核和孤束核。然而,尽管视前内侧区、下丘脑室周核、下丘脑室旁核、视交叉后区、VMH背内侧亚区、下丘脑外侧区、下丘脑背内侧核和乳头体前腹核含有大量催乳素反应性神经元,但这些区域显示很少有表达ERα mRNA的pSTAT5免疫反应性细胞。其次,我们评估了去卵巢小鼠对催乳素的敏感性,观察到性激素对于正常的催乳素反应性是必需的,因为与性腺完整的雌性小鼠相比,去卵巢小鼠在所有分析的脑核中催乳素诱导的pSTAT5免疫反应性神经元数量较少。此外,我们进行了下丘脑基因表达分析,以确定去卵巢后催乳素信号通路成分可能发生的变化。我们观察到催乳素受体、STAT5a或STAT5b的mRNA表达没有显著变化。总之,性激素在维持大脑对催乳素的敏感性方面发挥允许作用,最有可能是通过转录后机制。