Turi A, Kiss A L, Müllner N
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis Medical University, Budapest 8, H-1444, Hungary.
Cell Biol Int. 2001;25(8):785-94. doi: 10.1006/cbir.2001.0769.
Estrogen and progesterone, while regulating uterine functions, also regulate the number of caveolae and the level of caveolin. Large numbers of caveolae, as well as elevated expression of caveolin-1 and caveolin-2 isoforms in the myometrium of ovariectomised (OVX) rats were detected. 17beta-estradiol (E2) has a downregulating effect: the treatment of OVX rats with E2 (5 microg/animal) reduced the formation of caveolae by approx. 90%. Western blots clearly demonstrated the reduction of membrane caveolin-1 and -2 content. Progesterone treatment (2.5 mg/animal) alone did not cause any substantial change, but prevented the effect of estrogen. Control experiments showed that the quantity of Na+/K+-ATPase, a plasma membrane protein excluded from caveolae, was not downregulated by E2. The administration of the pure estrogen receptor (ERalpha) antagonist ICI 182,780 (1 mg/animal) not only compensated for the inhibitory effect of E2, but further increased the level of caveolin-1 in the myometrium of OVX rats and facilitated the formation of caveolae by approximately 70%. In contrast, the partial antagonist tamoxifen (1 mg/animal) mimicked the effect of estrogen. The amount of caveolin also changed during pregnancy. During the first half of pregnancy the expression of caveolin was suppressed, but it gradually increased until delivery. Our results indicate that the formation and number of caveolae are influenced by the physiological state of the uterus in a hormone dependent manner.
雌激素和孕激素在调节子宫功能的同时,也调节小窝的数量和小窝蛋白的水平。在去卵巢(OVX)大鼠的子宫肌层中检测到大量小窝,以及小窝蛋白-1和小窝蛋白-2亚型的表达升高。17β-雌二醇(E2)具有下调作用:用E2(5微克/只动物)处理OVX大鼠可使小窝的形成减少约90%。蛋白质免疫印迹法清楚地显示了膜小窝蛋白-1和-2含量的减少。单独给予孕激素(2.5毫克/只动物)未引起任何实质性变化,但可阻止雌激素的作用。对照实验表明,质膜蛋白钠钾ATP酶(一种不包含在小窝中的蛋白)的量并未因E2而下调。给予纯雌激素受体(ERα)拮抗剂ICI 182,780(1毫克/只动物)不仅可补偿E2的抑制作用,还可进一步提高OVX大鼠子宫肌层中小窝蛋白-1的水平,并使小窝的形成增加约70%。相反,部分拮抗剂他莫昔芬(1毫克/只动物)模拟了雌激素的作用。在怀孕期间小窝蛋白的量也会发生变化。在怀孕的前半期,小窝蛋白的表达受到抑制,但在分娩前会逐渐增加。我们的结果表明,小窝的形成和数量受子宫生理状态的激素依赖性影响。