Ing N H, Tornesi M B
Department of Animal Science, Institute of Biosciences and Technology, Texas A&M University, College Station 77843-2471, USA.
Biol Reprod. 1997 May;56(5):1205-15. doi: 10.1095/biolreprod56.5.1205.
The regulation of estrogen receptor (ER) and progesterone receptor (PR) genes is critical to estrogen and progesterone responsiveness of the uterus during the estrous cycle. A low dose of estradiol, given to ovariectomized ewes to mimic the preovulatory estrogen surge, acutely enhanced ER and PR gene expression in most uterine cells. Estradiol effects were measured at 12, 24, and 48 h post-injection (n = 6 ewes per time) with immunohistochemistry and in situ hybridization. Whereas vehicle-treated ovariectomized ewes demonstrated low to moderate ER and PR mRNA and protein expression, estradiol enhanced PR mRNA and protein expression (at 12 h and 24 h, respectively) more rapidly than ER mRNA and protein expression (at 24 h and 48 h, respectively) in most uterine cells. However, the timing and extent of the estradiol response depended partly upon cell type (epithelial, stromal, or myometrial), cell region (luminal, superficial, middle, or deep endometrial or myometrial), adjacent cells, and prior progesterone treatment. For example, PR mRNA up-regulation was prolonged in middle and deep endometrial stroma, but increases in PR protein expression were highest in superficial and middle endometrial compartments, including the luminal epithelium. The luminal epithelium and myometrium were unique in that estradiol failed to up-regulate ER gene expression within them. ER mRNA levels rose within these compartments only when estradiol followed steroid hormone treatment designed to induce an artificial estrous cycle (estradiol-progesterone-estradiol [EPE] treatment). The EPE treatment also augmented the rise in ER mRNA concentrations within stromal cells compared to estradiol treatment alone. Within uterine cell compartments, subpopulations of adjacent cells showed distinct estradiol responses, e.g., very high levels of ER and PR gene expression within stromal cells directly underlying glandular epithelial cells. Because the estradiol response did not always correlate with initial ER protein levels and was partly dependent upon cell compartment and adjacent cells, we must conclude that direct transcriptional and/or posttranscriptional actions of estradiol cooperate with other cellular and paracrine regulatory factors to regulate ER and PR gene expression and, thus, the steroid responsiveness of uterine cells.
雌激素受体（ER）和孕激素受体（PR）基因的调控对于发情周期中子宫对雌激素和孕激素的反应至关重要。给去卵巢母羊注射低剂量雌二醇以模拟排卵前的雌激素激增，可在大多数子宫细胞中急性增强ER和PR基因表达。在注射后12、24和48小时（每次n = 6只母羊），采用免疫组织化学和原位杂交法测定雌二醇的作用。虽然接受载体处理的去卵巢母羊显示出低至中等水平的ER和PR mRNA及蛋白表达，但在大多数子宫细胞中，雌二醇增强PR mRNA和蛋白表达（分别在12小时和24小时）的速度比增强ER mRNA和蛋白表达（分别在24小时和48小时）更快。然而，雌二醇反应的时间和程度部分取决于细胞类型（上皮、基质或肌层）、细胞区域（腔面、浅层、中层或深层子宫内膜或肌层）、相邻细胞以及先前的孕激素处理。例如，PR mRNA上调在中层和深层子宫内膜基质中持续时间较长，但PR蛋白表达增加在浅层和中层子宫内膜区域（包括腔上皮）最高。腔上皮和肌层的独特之处在于，雌二醇未能在其中上调ER基因表达。只有当雌二醇在旨在诱导人工发情周期的类固醇激素处理（雌二醇 - 孕激素 - 雌二醇 [EPE] 处理）之后时，这些区域内的ER mRNA水平才会升高。与单独使用雌二醇处理相比，EPE处理还增强了基质细胞中ER mRNA浓度的升高。在子宫细胞区域内，相邻细胞亚群表现出不同的雌二醇反应，例如，腺上皮细胞正下方的基质细胞内ER和PR基因表达水平非常高。由于雌二醇反应并不总是与初始ER蛋白水平相关，且部分取决于细胞区域和相邻细胞，我们必须得出结论，雌二醇的直接转录和/或转录后作用与其他细胞和旁分泌调节因子协同作用，以调节ER和PR基因表达，从而调节子宫细胞的类固醇反应性。
