Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Stritch School of Medicine, Maywood, Illinois 60153.
Mol Cell Neurosci. 1993 Apr;4(2):191-8. doi: 10.1006/mcne.1993.1023.
The influence of estrogen (E) on corticosterone (CORT) receptor function in neural tissue was investigated in female Sprague-Dawley rats. This was accomplished by using a sensitive solution-hybridization RNase protection assay to examine the effect of E on the regulation of CORT receptor mRNAs. Animals were bilaterally ovariectomized (OVX), and a Silastic capsule (0.5 cm) containing 17beta-estradiol was sc implanted. Control animals received a blank capsule. Animals were killed 1, 7, or 21 days later. Anterior pituitary glucocorticoid receptor (GR) mRNA levels were significantly lower (P < 0.01) in E-treated rats at all time points examined. Hippocampal GR mRNA levels were significantly decreased below OVX values (P < 0.01) after 1 and 21 days of E treatment. Hypothalamic-preoptic area (HPOA) GR mRNA levels were significantly lower (P < 0.01) than OVX values only after 21 days of E treatment. Mineralocorticoid receptor mRNA levels were significantly lower after E treatment (P < 0.01) at all time points and in all three tissues examined. In a second study, we administered the GR-specific agonist RU 28362 (40 mug/100 g BW for 4 days) or the nonspecific agonist dexamethasone (DEX; 40 mug/100 g BW for 4 days) to OVX - and OVX + E-treated animals. The administration of RU 28362 significantly down-regulated hippocampal GR mRNA (P < 0.05) in OVX rats only. In contrast, DEX administration significantly down-regulated hippocampal GR mRNA (P < 0.05) in both control and E-treated animals. The administration of DEX or RU 28362 significantly reduced GR mRNA levels (P < 0.05) in the HPOA of OVX control animals, but not E-treated animals. Thus, E treatment results in a loss of the glucocorticoid receptor's ability to down-regulate its mRNA. These studies, combined with our earlier findings that E treatment impairs the ability of GR to down-regulate its protein (8), provide evidence that E interferes with glucocorticoid receptor function.
本研究旨在探讨雌激素（E）对神经组织中皮质酮（CORT）受体功能的影响。采用敏感的溶液杂交 RNA 保护分析法，观察 E 对 CORT 受体 mRNA 调节的影响。动物双侧卵巢切除（OVX）后，皮下植入含有 17β-雌二醇的 Silastic 胶囊（0.5cm）。对照组动物植入空白胶囊。1、7 或 21 天后处死动物。所有检测时间点，E 处理组动物的垂体前叶糖皮质激素受体（GR）mRNA 水平均显著降低（P<0.01）。E 处理 1 和 21 天后，海马 GRmRNA 水平明显低于 OVX 值（P<0.01）。E 处理 21 天后，下丘脑-视前区（HPOA）GRmRNA 水平明显低于 OVX 值（P<0.01）。所有检测时间点和所有三种组织中，E 处理后盐皮质激素受体 mRNA 水平均显著降低（P<0.01）。在第二项研究中，我们给予 GR 特异性激动剂 RU28362（40μg/100gBW，连续 4 天）或非特异性激动剂地塞米松（DEX；40μg/100gBW，连续 4 天）处理 OVX 和 OVX+E 处理的动物。RU28362 给药显著下调 OVX 大鼠海马 GRmRNA（P<0.05）。相反，DEX 给药显著下调对照组和 E 处理组动物的海马 GRmRNA（P<0.05）。DEX 或 RU28362 给药显著降低 OVX 对照组动物 HPOA 的 GRmRNA 水平（P<0.05），但不影响 E 处理的动物。因此，E 处理导致糖皮质激素受体下调其 mRNA 的能力丧失。这些研究与我们早期的发现相结合，即 E 处理损害了 GR 下调其蛋白的能力（8），提供了 E 干扰糖皮质激素受体功能的证据。
