Control of uterine estrogen receptor levels by progesterone.
Control of uterine estrogen receptor levels by progesterone.
复制标题
通过黄体酮控制子宫雌激素受体水平。
作者：
A. Hsueh;E. Peck;James H. Clark
在未成熟大鼠中检查了黄体酮拮抗雌激素对子宫生长的刺激的机制。大鼠每天注射 2.5 杯雌二醇 (E)，持续 2 天，第 3 天注射 2.5 杯 E 或 2.5 杯 E 加 2.5 毫克黄体酮 (P)。注射E或E+P后不同时间间隔通过[3H]雌二醇交换测定核和细胞质雌激素受体的数量。在两组中，核受体雌激素复合物(RnE)在注射后1小时急剧增加，并在注射后4至24小时逐渐下降。两组细胞质受体Rc的数量在1小时内降至低水平，并在4至8小时内开始逐渐增加。然而，注射后8至24小时之间，E治疗组的Rc水平继续增加（24小时时为2.39+/-0.21pmol/子宫），但E+P组中的Rc水平保持在8小时水平（24小时时为1.09+/-0.04pmol/子宫）。这一观察结果表明，Rc 的补充涉及两个独立的过程，并且黄体酮抑制第二阶段的补充。 E+P预处理后Rc对雌激素的结合亲和力和特异性与E预处理组相同。因此，P 不会改变结合特性，而是会改变 Rc 的宫内水平。第 4 天用 E 治疗，此时 E 组和 E + P 组之间的 Rc 水平不同，E 预处理组在第 5 天刺激了子宫重量和蛋白质含量。然而，在 E+P 预处理组中观察到的刺激最小。 E组第4天E注射后RnE的数量和RnE核保留时间均大于E+P组。黄体酮对 Rc 补充的影响是剂量依赖性的（范围，0.1-2.5 mg；最大 1/2，0.5 mg）。在第 3 天注射丙酸睾酮（1.0 毫克）（一种弱雌激素拮抗剂），导致第 4 天的 Rc 水平略有降低。这种降低也与第 4 天对 E 治疗的敏感性降低相关。这些数据与我们实验室之前的研究一起表明，黄体酮和其他雌激素拮抗剂（如萘福定和丙酸睾酮）通过干扰 Rc 的补充来抑制雌激素作用，从而减少子宫核易位和保留的雌激素受体复合物的数量。
The mechanism by which progesterone antagonizes estrogenic stimulation of uterine growth was examined in the immature rat. Rats received daily injections of 2.5 mug estradiol (E) for 2 days and on day 3 either 2.5 mug E or 2.5 mug E plus 2.5 mg of progesterone (P). The quantity of nuclear and cytoplasmic estrogen receptor was determined by [3H]estradiol exchange at various intervals after injection of E or E + P. In both groups, nuclear receptor estrogen complex (RnE) increased dramtically one hour after injection and showed a gradual decline from 4 to 24 h after injection. The quantity of cytoplasmic receptor, Rc, decreased to low levels by one hour and began a gradual increase from 4 to 8 h in both groups. However, between 8 and 24 h after injection, the level of Rc continued to increase in the E treatment group (2.39 +/- 0.21 pmol/uterus at 24 h) but remained at the 8 h level in the E + P group (1.09 +/- 0.04 pmol/uterus at 24 h). This observation suggests that two seperate processes are involved in the replenishment of Rc and that progesterone inhibits the second phase of replenishment. The binding affinity and specificity of Rc for estrogens following E + P pretreatment were identical to those of the E pretreatment group. Therefore, P does not alter the binding properties but rather the intrauterine level of Rc. Treatment with E on day 4, when Rc levels differ between E and E + P groups, stimulated uterine weight and protein content on day 5 in the E pretreatment group. However, minimal stimulation was observed in the E + P pretreatment group. The quantity of RnE and the time of nuclear retention of RnE following E injection on day 4 was greater in the E group than in the E + P group. The effect of progesterone on Rc replenishment was dose-dependent (range, 0.1-2.5 mg; 1/2 maximal, 0.5 mg). Injection of testosterone propionate (1.0 mg), a weak estrogen antagonist, with E on day 3 resulted in slightly reduced levels of Rc on day 4. This reduction also correlated with a reduced sensitivity to treatment with E on day 4. These data, together with previous studies from our laboratory, suggest that progesterone and other estrogen antagonists such as nafoxidine and testosterone propionate inhibit estrogen action by interfering with the replenishment of Rc, thereby reducing the number of receptor estrogen complexes that are translocated and retained by uterine nuclei.