Cellular and molecular study of sex steroid- and growth factor-mediated regulatory mechanism of mouse uterine endometrial cells

哺乳动物子宫内膜细胞的增殖受卵巢性类固醇和生长因子的调节。子宫内膜由单层上皮细胞层和下层基质细胞层组成。在这种小鼠子宫内膜细胞的三维培养系统中，上皮细胞的增殖由于下层基质细胞的存在而增加。该结果表明，基质细胞影响上皮细胞功能，包括细胞生长。基质细胞分泌表皮生长因子（EGF）、转化生长因子-α（TGF-α）和EGF受体（EGF-R）。EGF和TGF-α刺激基质细胞增殖。雌二醇和孕酮的联合治疗也刺激了基质细胞的增殖，但EGF-R的特异性抑制剂RG-13022抵消了雌二醇和孕酮的刺激作用。雌二醇和孕酮联合治疗增加TGF-α mRNA水平，但不增加EGF mRNA水平。EGF-R mRNA水平的增强雌二醇和孕酮的联合治疗。这些结果表明，基质细胞的生长受到雌二醇和孕酮的调节，这种作用是由TGF-α介导的。本研究表明，TGF-α的旁分泌作用可刺激小鼠子宫内膜间质细胞的增殖，而TGF-α在间质细胞中的合成受卵巢雌激素和孕激素的调节。

Proliferation of mammalian uterine endometrial cells is regulated by ovarian sex steroids and growth factors. Uterine endometrium consists of a single epithelial cell layer and the underlying stromal cell layer, The mouse endometrium was reorganized in vitro culture system. In this three-dimensional culture system of mouse endometrial cells, the proliferation of the epithelial cells was increased by the presence of the underlying stromal cells. This result suggests that the stromal cells affect epithelial cell functions including the cell growth. The stromal cells produced epidermal growth factor (EGF), transforming growth factor -α(TGF-α) and EGF-receptors (EGF-R). EGF and TGF-α stimulated the proliferation of stromal cells. A combined treatment of estradiol and progesterone also stimulated the proliferation of stromal cells, but RG-13022, a specific inhibitor of EGF-R, nullified the stimulatory effect of estradiol and progesterone. A combined treatment of estradiol and progesterone increased TGF-α mRNA levels, but not EGF mRNA levels. EGF-R mRNA levels was enhanced by a combined treatment of estradiol and progesterone. These results indicate that the growth of stromal cells was regulated by estradiol and progesterone, and this action was mediated by TGF-α. The present study demonstrated that proliferation of mouse uterine endometrial stromal cells was stimulated by a paracrine action of TGF-α, whose synthesis in the stromal cells was regulated by ovarian estrogen and progesterone.