Blaustein J D
Brain Res. 1987 Feb 24;404(1-2):39-50. doi: 10.1016/0006-8993(87)91353-9.
A series of experiments was performed to determine the effects of the alpha 1-noradrenergic antagonist, prazosin, on the concentration of estrogen receptors in female rat brain and pituitary gland. Prazosin caused a dose-dependent decrease in the concentration of cytosol estrogen receptors in mediobasal hypothalamus when injected 10 and 16 h prior to assay. The drug was without effect on the concentration of nuclear estrogen receptors in the absence of estradiol, indicating that the decreased concentration of cytosol estrogen receptors is not due to nuclear estrogen receptor accumulation. Scatchard analysis confirmed that prazosin treatment decreases the concentration of cytosol estrogen receptors without influencing the apparent affinity of the receptors for [3H]estradiol. The prazosin-induced decrease in the concentration of cytosol estrogen receptors in the mediobasal hypothalamus was transient with maximal effects occurring between 8 and 12 h after a single injection. Competition analysis confirmed that prazosin is not an effective competitor for binding to the estrogen receptor in vitro. The effects of prazosin on the estrogen receptor system could not be attributed to modulation of the levels of norepinephrine or dopamine. Assay of the levels of norepinephrine and dopamine in hypothalamus and preoptic area after prazosin injection revealed no effects of prazosin on the level of either of these catecholamines. An estradiol injection resulted in the predicted decrease in the concentration of estrogen receptors accumulating in hypothalamic cell nuclei, suggesting that the cytosol estrogen receptors that decrease in concentration are functional receptors. Prazosin treatment did not result in a decrease in the effectiveness of estradiol in the induction of cytosol progestin receptors in the mediobasal hypothalamus, suggesting that the cells are regulated by the alpha 1-noradrenergic system may not be those cells in which progestin receptors are also induced. These experiments provide further evidence that the noradrenergic system modulates the concentration of estrogen receptors, and perhaps sensitivity to estradiol, in some cells within the rat hypothalamus.
进行了一系列实验以确定α1 - 去甲肾上腺素能拮抗剂哌唑嗪对雌性大鼠脑和垂体中雌激素受体浓度的影响。在检测前10小时和16小时注射哌唑嗪时，它会导致中基底下丘脑细胞质雌激素受体浓度呈剂量依赖性降低。在没有雌二醇的情况下，该药物对核雌激素受体浓度没有影响，这表明细胞质雌激素受体浓度的降低不是由于核雌激素受体的积累。Scatchard分析证实，哌唑嗪处理可降低细胞质雌激素受体浓度，而不影响受体对[3H]雌二醇的表观亲和力。哌唑嗪诱导的中基底下丘脑细胞质雌激素受体浓度降低是短暂的，单次注射后8至12小时出现最大效应。竞争分析证实，哌唑嗪在体外不是与雌激素受体结合的有效竞争者。哌唑嗪对雌激素受体系统的影响不能归因于去甲肾上腺素或多巴胺水平的调节。注射哌唑嗪后对下丘脑和视前区去甲肾上腺素和多巴胺水平的检测显示，哌唑嗪对这两种儿茶酚胺的水平均无影响。注射雌二醇导致下丘脑细胞核中积累的雌激素受体浓度如预期般降低，这表明浓度降低的细胞质雌激素受体是功能性受体。哌唑嗪处理并未导致雌二醇诱导中基底下丘脑细胞质孕激素受体有效性的降低，这表明受α1 - 去甲肾上腺素能系统调节的细胞可能不是同时诱导孕激素受体的细胞。这些实验进一步证明，去甲肾上腺素能系统调节大鼠下丘脑某些细胞中雌激素受体的浓度，也许还调节对雌二醇的敏感性。
