Gunin A G, Mashin I N, Zakharov D A
Department of Histology, Medical Institute, Chuvash State University, PO Box 86, Cheboksary 428034, Russia.
J Endocrinol. 2001 Apr;169(1):23-31. doi: 10.1677/joe.0.1690023.
Glucocorticoids have been known to be involved in the regulation of some aspects of estrogen action on the uterus. However, the effect of glucocorticoids on changes in uterine morphogens produced by chronic estrogen exposure is not known. Therefore, the aim of this work was to examine the role of glucocorticoids on proliferative and morphogenetic uterine reactions induced by continuous estrogen treatment. Ovariectomized mice received subcutaneous injections of estradiol dipropionate in olive oil (2 microg per 100 g body weight once a week) or vehicle and drank water with or without dexamethasone (2 mg/l) for 30, 60 and 90 days. Treatment with dexamethasone caused a marked reduction in estradiol-induced changes in uterine weight, in proliferation (estimated from the proportion of mitotic and BrdU-labeled cells in all uterine tissues), and in changes in estradiol-dependent morphogenesis, which was redirected from the formation of atypical hyperplasia in animals receiving only estradiol to the appearance of simple or cystic endometrial hyperplasia in animals receiving both estradiol and dexamethasone. Estradiol alone increased dramatically the number of perpendicular oriented mitoses in luminal and glandular epithelia, and administration of dexamethasone inhibited this effect. In the absence of estradiol, chronic treatment with dexamethasone has no effect on all uterine parameters tested. Thus, chronic glucocorticoid treatment produces a complex antiestrogenic effect in the uterus of mice. Estradiol-induced changes in mitosis orientation are probably responsible for changes in the shape of glands and development of endometrial hyperplasia.
已知糖皮质激素参与雌激素对子宫作用某些方面的调节。然而，糖皮质激素对慢性雌激素暴露所产生的子宫形态发生素变化的影响尚不清楚。因此，本研究的目的是探讨糖皮质激素在持续雌激素治疗诱导的子宫增殖和形态发生反应中的作用。对去卵巢小鼠皮下注射溶于橄榄油的二丙酸雌二醇（每100 g体重2 μg，每周一次）或溶剂，并饮用含或不含地塞米松（2 mg/l）的水，持续30、60和90天。地塞米松治疗显著降低了雌二醇诱导的子宫重量变化、增殖（根据所有子宫组织中有丝分裂和BrdU标记细胞的比例估算）以及雌二醇依赖性形态发生的变化，形态发生变化从仅接受雌二醇的动物中的非典型增生形成转变为同时接受雌二醇和地塞米松的动物中的单纯性或囊性子宫内膜增生。单独使用雌二醇可显著增加腔上皮和腺上皮中垂直取向的有丝分裂数量，而地塞米松的给药可抑制这种作用。在没有雌二醇的情况下，地塞米松的慢性治疗对所有测试的子宫参数均无影响。因此，慢性糖皮质激素治疗在小鼠子宫中产生复杂的抗雌激素作用。雌二醇诱导的有丝分裂方向变化可能是腺体形状改变和子宫内膜增生发展的原因。
