Rhen Turk, Grissom Sherry, Afshari Cynthia, Cidlowski John A
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Dr., Research Triangle Park, North Carolina 27709, USA.
FASEB J. 2003 Oct;17(13):1849-70. doi: 10.1096/fj.02-1099com.
Estrogens and glucocorticoids have opposing effects on the female reproductive tract, but the molecular basis for this antagonism is poorly understood. We therefore examined the biological and transcriptional programs induced by estrogens and glucocorticoids in the uterus of immature female rats. Estradiol 17beta (E2) rapidly induced morphological changes reminiscent of an acute inflammatory response, including infiltration of eosinophils, edema in the stroma and myometrium, and a decrease in the height of luminal epithelial cells, whereas dexamethasone (Dex) only altered stromal cell morphology. When coadministered with E2, Dex completely blocked the proinflammatory effects of E2. Surprisingly, examination of E2 and Dex effects on gene expression using cDNA microarrays and real-time PCR revealed that these hormones had similar effects on the expression of many genes and that very few genes displayed antagonistic regulation. Together, these results indicate strong discord between the early biologic and genomic actions of estrogens and glucocorticoids and highlight a complex regulatory role for glucocorticoids and GR in the mammalian uterus.
雌激素和糖皮质激素对雌性生殖道具有相反的作用，但其拮抗作用的分子基础仍知之甚少。因此，我们研究了未成熟雌性大鼠子宫中雌激素和糖皮质激素诱导的生物学和转录程序。17β-雌二醇（E2）迅速诱导出类似于急性炎症反应的形态学变化，包括嗜酸性粒细胞浸润、基质和子宫肌层水肿以及腔上皮细胞高度降低，而地塞米松（Dex）仅改变基质细胞形态。与E2共同给药时，Dex完全阻断了E2的促炎作用。令人惊讶的是，使用cDNA微阵列和实时PCR检测E2和Dex对基因表达的影响发现，这些激素对许多基因的表达具有相似的作用，很少有基因表现出拮抗调节。这些结果共同表明，雌激素和糖皮质激素的早期生物学和基因组作用之间存在强烈的不一致，并突出了糖皮质激素和糖皮质激素受体（GR）在哺乳动物子宫中的复杂调节作用。
