Khan S A, Moulton B C
Department of Anatomy, University of Cincinnati, College of Medicine, OH 45267-0521.
J Steroid Biochem. 1990 May;35(6):701-4. doi: 10.1016/0022-4731(90)90310-o.
Initiation of uterine DNA synthesis and mitosis in response to estrogen appears to depend upon the stimulation of protein synthesis. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase could have a key function in controlling uterine mitosis through its control of mevalonic acid and cholesterol synthesis as the rate-limiting enzyme in their synthetic pathways. These studies were initiated to examine the kinetics of the uterine increases in HMG-CoA reductase activity in response to estradiol. In the uterus of the ovariectomized mature rat, estradiol increased levels of enzyme activity in both the luminal epithelium and stroma-myometrium up to 12 h after estradiol treatment. Levels of HMG-CoA reductase activity decreased after 12 h in the luminal epithelium and further increased in the stroma-myometrium. Previous studies have shown that estradiol does not increase DNA synthesis and mitosis in the stroma-myometrium of the uterus of the ovariectomized mature rat. Since estradiol increased HMG-CoA reductase activity in both the luminal epithelium and stroma-myometrium, we conclude that even though increased HMG-CoA reductase activity may be a prerequisite for increased DNA synthesis, increases in uterine HMG-CoA reductase activity are not necessarily followed by increased DNA synthesis.
子宫对雌激素作出反应启动DNA合成和有丝分裂似乎依赖于蛋白质合成的刺激。3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶作为甲羟戊酸和胆固醇合成途径中的限速酶，通过控制它们的合成可能在控制子宫有丝分裂中起关键作用。开展这些研究是为了检测子宫中HMG-CoA还原酶活性对雌二醇反应的动力学变化。在去卵巢成熟大鼠的子宫中，雌二醇处理后长达12小时，管腔上皮和基质-肌层中的酶活性水平均升高。管腔上皮中HMG-CoA还原酶活性水平在12小时后下降，而基质-肌层中则进一步升高。先前的研究表明，雌二醇不会增加去卵巢成熟大鼠子宫基质-肌层中的DNA合成和有丝分裂。由于雌二醇增加了管腔上皮和基质-肌层中HMG-CoA还原酶的活性，我们得出结论，即使HMG-CoA还原酶活性增加可能是DNA合成增加的先决条件，但子宫中HMG-CoA还原酶活性增加不一定会导致DNA合成增加。
