Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Neurochem Res. 2013 Jan;38(1):82-9. doi: 10.1007/s11064-012-0891-1. Epub 2012 Sep 18.
The activation of the subtype α of estrogen receptors (ERα) in the hypothalamic ventromedial nucleus (VMNvl) is required to stimulate female sexual receptivity. Moreover, the hormone was found to govern the expression of the receptor. Its removal due to ovariectomy and subsequent substitution suggest that the hormone down-regulates the expression of ERα. In contrast, in normally cycling animals the expression of the receptor peaks at proestrus, the phase of highest concentration of 17β-estradiol in estrous cycle. Therefore, in this study we examined the influence of the hormone on ERα expression in primary dissociated cultures of neurons isolated from the VMNvl of young adult female rats. Measurements of ERα immunofluorescence revealed that both supraphysiological and physiological concentrations of 17β-estradiol increase the expression of ERα. Analyses with selective agonists showed that both nuclear ERs are able to mediate the action of the hormone. However, the activation of ERα had a stronger effect on the expression of its own receptor than the activation of ERβ. Simultaneous activation of both receptors attenuated the influence of ERα alone. Physiological concentrations of progesterone were found to revoke the effect of 17β-estradiol, whereas the expression of ERα is up-regulated by progesterone alone. These data indicate that the expression of ERα in VMNvl neurons is under the control of both types of nuclear ERs and, in addition, progesterone receptors (PRs). The particular contribution of the receptors is dependent on their level of expression and the hormonal context. In neurons expressing high quantity of ERα, ERβ attenuates the overall expression of the receptor, whereas in cells containing mostly ERβ it contributes to the up-regulation of ERα synthesis. Simultaneous activation of ERs and PRs reverses the influences of the receptors due to inter-inhibition of their transcriptional activities.
雌激素受体（ER）亚型 α 在下丘脑腹内侧核（VMNvl）的激活对于刺激雌性性接受性是必需的。此外，该激素被发现可以控制受体的表达。由于卵巢切除和随后的替代，激素的去除表明激素下调 ERα 的表达。相比之下，在正常循环的动物中，受体的表达在发情前期达到峰值，即发情周期中 17β-雌二醇浓度最高的阶段。因此，在这项研究中，我们检查了激素对来自年轻成年雌性大鼠 VMNvl 的神经元原代分离培养物中 ERα 表达的影响。ERα 免疫荧光测量显示，超生理和生理浓度的 17β-雌二醇均增加 ERα 的表达。用选择性激动剂进行的分析表明，核 ER 均能够介导激素的作用。然而，ERα 的激活对其自身受体的表达具有比 ERβ 的激活更强的影响。两种受体的同时激活减弱了 ERα 单独激活的影响。发现生理浓度的孕酮可撤销 17β-雌二醇的作用，而孕酮单独可上调 ERα 的表达。这些数据表明，VMNvl 神经元中 ERα 的表达受到两种类型的核 ER 以及孕酮受体（PR）的控制。受体的特定贡献取决于它们的表达水平和激素环境。在表达大量 ERα 的神经元中，ERβ 减弱了受体的整体表达，而在主要含有 ERβ 的细胞中，它有助于 ERα 合成的上调。ER 和 PR 的同时激活由于其转录活性的相互抑制而逆转了受体的影响。
