Sakaguchi Hideki, Fujimoto Jiro, Aoki Ikumi, Tamaya Teruhiko
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan.
Steroids. 2003 Jan;68(1):11-9. doi: 10.1016/s0039-128x(02)00111-3.
Although a clear role for estrogen receptor (ER) alpha has been established, the contribution of ERbeta in estrogen-dependent development, growth and functions of the myometrium is not understood. As a first step towards understanding the role of ERbeta, we have examined the expression of ERalpha and ERbeta in the human myometrium. With competitive RT-PCR assays, the level of ERbeta mRNA was 10-200 times lower than that of ERalpha mRNA in both premenopausal and postmenopausal myometrium. In premenopausal myometrium, the expression pattern of ERbeta mRNA during the menstrual cycle was similar to that of ERalpha mRNA, with highest levels in peri-ovulatory phase. In postmenopausal myometrium, ERbeta mRNA was significantly higher than it was in premenopausal myometrium, while the level of ERalpha mRNA was lower. The net result was a change in the ratio of ERbeta to ERalpha mRNA expression. The ratio changed from 0.6-1.5 in premenopausal to 2.5-7.6 in postmenopausal myometrium. In premenopausal women, the gonadotropin releasing hormone analogue, leuprorelin acetate, elicited a decrease in ERalpha and an increase in ERbeta mRNA expression to cause a postmenopausal receptor phenotype. Estradiol, on the other hand, reversed ERalpha and ERbeta mRNA expression and their ratio in postmenopausal myometrium to those of premenopausal myometrium. Immunohistochemical staining and Western blot analysis of ERalpha and ERbeta with semiquantitative analysis showed good agreement between mRNA and protein levels. The data indicate that coordinated expression of ERalpha and ERbeta might be necessary for normal estrogen action in myometrium. Furthermore, estrogen appears a dominant regulator of both receptors in the myometrium.
尽管雌激素受体（ER）α的明确作用已得到证实，但ERβ在子宫肌层雌激素依赖性发育、生长和功能中的作用尚不清楚。作为了解ERβ作用的第一步，我们检测了ERα和ERβ在人子宫肌层中的表达。通过竞争性逆转录-聚合酶链反应（RT-PCR）分析，绝经前和绝经后子宫肌层中ERβ mRNA的水平均比ERα mRNA低10至200倍。在绝经前子宫肌层中，月经周期中ERβ mRNA的表达模式与ERα mRNA相似，在排卵期周围水平最高。在绝经后子宫肌层中，ERβ mRNA明显高于绝经前子宫肌层，而ERα mRNA水平较低。最终结果是ERβ与ERα mRNA表达比例发生变化。该比例从绝经前的0.6至1.5变为绝经后的2.5至7.6。在绝经前女性中，促性腺激素释放激素类似物醋酸亮丙瑞林可使ERα减少，ERβ mRNA表达增加，从而导致绝经后受体表型。另一方面，雌二醇可使绝经后子宫肌层中ERα和ERβ mRNA表达及其比例恢复到绝经前子宫肌层的水平。对ERα和ERβ进行免疫组织化学染色及蛋白质印迹分析并进行半定量分析，结果显示mRNA水平与蛋白质水平具有良好的一致性。数据表明，ERα和ERβ的协同表达可能是子宫肌层正常雌激素作用所必需的。此外，雌激素似乎是子宫肌层中这两种受体的主要调节因子。
