Department of Physiology and Endocrinology, Medical College of Georgia, Augusta, Georgia 30912-3000, USA.
Mol Cell Neurosci. 1992 Dec;3(6):487-96. doi: 10.1016/1044-7431(92)90061-6.
Previous work from our laboratory has demonstrated that progesterone can induce a rapid decrease in estrogen receptor (ER) binding in the anterior pituitary of the rat. This effect of progesterone on ER correlates well with the loss of estrogen action. The objectives of this study were to determine whether the rapid decrease in ER binding in the rat pituitary after a single injection of estradiol and the decrease in ER binding induced by progesterone in the estrogen-primed rat could be due to a suppression of mRNA levels for the estrogen receptor. Ovariectomy for 14 days decreased ER mRNA levels and injection of 2 mug of estradiol in ethanol:saline for 3 days increased ER mRNA levels. A single injection of 1 mug of estradiol brought about no change in ER mRNA levels in the pituitary of ovariectomized rats within 1 h of administration. Five micrograms of estradiol increased the ER mRNA levels, whereas 10 mug of estradiol brought about a decrease in ER mRNA levels. Thus, the reported decrease in pituitary ER binding after 1 and 5 mug of estradiol was not accompanied by a similar change in ER mRNA levels, suggesting that the decrease in ER binding may be due to accelerated processing of ER or to decreased translation of ER mRNA. When 2 mug of estradiol was injected into estrogen-primed ovariectomized rats, the recovery of ER binding at 18 h was preceded by an increase in ER mRNA levels at 12 h, suggesting new ER synthesis during the recovery process. Progesterone (0.8 mg/kg body wt), in the absence of estradiol-priming, increased ER mRNA levels in the pituitary at 1, 6, and 12 h and decreased them at 18 h. In estrogen-primed animals, the changes in ER mRNA levels brought about by progesterone combined with estradiol were similar to those observed with estradiol alone, with the exception that ER mRNA levels were elevated in the progesterone-treated group at 1 h, a time when ER binding was further suppressed. Thus the progesterone-induced decrease in ER binding was not due to a suppression of ER mRNA levels. In estrogen-primed rats 0.8 and 4.0 mg/kg body wt doses of progesterone increased ER mRNA levels, whereas the 2.0 mg/kg body wt dose did not. These results indicate that estradiol alone has a time- and dose-dependent effect on ER mRNA levels in the anterior pituitary. Progesterone by itself and in the presence of estrogen priming has a dose-related effect on anterior pituitary ER mRNA levels. Furthermore, the effect of progesterone on decreasing ER binding appears to be due either to a post-transcriptional effect and/or to accelerated receptor processing.
先前我们实验室的工作表明，孕酮可以快速降低大鼠前垂体中的雌激素受体（ER）结合。孕酮对 ER 的这种作用与雌激素作用的丧失密切相关。本研究的目的是确定单次注射雌二醇后大鼠垂体中 ER 结合的快速下降，以及孕酮在雌激素预处理大鼠中诱导的 ER 结合下降是否是由于雌激素受体 mRNA 水平的抑制所致。卵巢切除术 14 天降低 ER mRNA 水平，2 微克雌二醇在乙醇：盐水注射 3 天增加 ER mRNA 水平。在给予卵巢切除术大鼠 1 小时内，1 微克雌二醇单次注射不会改变垂体中的 ER mRNA 水平。5 微克雌二醇增加 ER mRNA 水平，而 10 微克雌二醇降低 ER mRNA 水平。因此，报告的 1 和 5 微克雌二醇后垂体 ER 结合的减少并没有伴随着 ER mRNA 水平的类似变化，这表明 ER 结合的减少可能是由于 ER 的加速处理或 ER mRNA 的翻译减少所致。当 2 微克雌二醇注射到雌激素预处理的卵巢切除大鼠中时，在 18 小时 ER 结合的恢复之前，在 12 小时时 ER mRNA 水平增加，这表明在恢复过程中存在新的 ER 合成。孕酮（0.8mg/kg 体重）在没有雌二醇预刺激的情况下，在 1、6 和 12 小时增加垂体中的 ER mRNA 水平，并在 18 小时降低它们。在雌激素预处理的动物中，孕酮与雌二醇联合引起的 ER mRNA 水平的变化与单独使用雌二醇时观察到的变化相似，只是在孕酮处理组中，在 ER 结合进一步受到抑制的 1 小时时，ER mRNA 水平升高。因此，孕酮诱导的 ER 结合减少不是由于 ER mRNA 水平的抑制。在雌激素预处理的大鼠中，0.8 和 4.0mg/kg 体重的孕酮剂量增加 ER mRNA 水平，而 2.0mg/kg 体重的剂量没有增加。这些结果表明，雌二醇单独对前垂体 ER mRNA 水平具有时间和剂量依赖性的影响。孕酮本身以及在雌激素预处理的情况下，对前垂体 ER mRNA 水平具有剂量依赖性的影响。此外，孕酮降低 ER 结合的作用似乎是由于转录后效应和/或受体的加速处理。
