Sá Susana I, Fonseca Bruno M, Teixeira Natércia, Madeira M Dulce
Department of Anatomy, Faculty of Medicine, University of Porto, Portugal; Center of Experimental Morphology (CME), Faculty of Medicine, University of Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Portugal.
FEBS J. 2015 Mar;282(6):1126-36. doi: 10.1111/febs.13207. Epub 2015 Feb 6.
Progesterone receptor (PR) activation in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is essential for promoting female sexual behavior. Estrogen receptor (ER) α, in contrast to ERβ, has been implicated in the induction of PRs. The simultaneous activation of ERα and ERβ, although not increasing the number of PR-immunoreactive neurons in the VMNvl, facilitates lordosis, which suggests that ERβ and/or the ERα-ERβ interaction might play a role in PR dynamics and/or PR expression by individual neurons. To address this question, we used western blot and immunohistochemical studies to determine the amounts and subcellular distributions of both PR isoforms in VMNvl neurons of ovariectomized rats injected with estradiol benzoate or with specific agonists of ERα and ERβ, alone or in association. The present data show that ERα activation does not change PR expression in individual neurons, but increases the number of PRs in the VMNvl, because it increases the number of neurons expressing PRs. Conversely, ERβ activation does not change the total number of PRs in the VMNvl, but increases the labeling intensity of the perikaryal cytoplasm, which suggests that it promotes the transport of PRs from neurites into cell bodies. In addition, the simultaneous activation of ERα and ERβ increases the expression of PRs by individual neurons and, consequently, increases the total number of PRs in the VMNvl. Our findings reveal that individual and simultaneous activation of ERα and ERβ have different effects on the levels and subcellular location of PRs in VMNvl neurons.
下丘脑腹内侧核腹外侧区(VMNvl)中的孕激素受体(PR)激活对于促进雌性性行为至关重要。与雌激素受体(ER)β相比,ERα与PR的诱导有关。ERα和ERβ的同时激活虽然不会增加VMNvl中PR免疫反应性神经元的数量,但会促进脊柱前凸,这表明ERβ和/或ERα-ERβ相互作用可能在单个神经元的PR动态变化和/或PR表达中发挥作用。为了解决这个问题,我们使用蛋白质印迹和免疫组织化学研究来确定单独或联合注射苯甲酸雌二醇或ERα和ERβ特异性激动剂的去卵巢大鼠VMNvl神经元中两种PR亚型的数量和亚细胞分布。目前的数据表明,ERα激活不会改变单个神经元中的PR表达,但会增加VMNvl中PR的数量,因为它增加了表达PR的神经元数量。相反,ERβ激活不会改变VMNvl中PR的总数,但会增加胞体细胞质的标记强度,这表明它促进了PR从神经突向细胞体的转运。此外,ERα和ERβ的同时激活会增加单个神经元中PR的表达,从而增加VMNvl中PR的总数。我们的研究结果表明,ERα和ERβ的单独激活和同时激活对VMNvl神经元中PR的水平和亚细胞定位有不同的影响。