HORMONAL REGULATION OF CULTURED ENDOMETRIAL CELLS

培养子宫内膜细胞的激素调节

• 批准号: 3166842
• 负责人: LAZARO E GERSCHENSON
• 金额: $ 14.56万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3166842
• 关键词: aminoacid transport; carbohydrate transport; cell cycle; cell differentiation; cyclic AMP; cyclic GMP; electrofocusing; endometrium; fluorimetry; gas chromatography; gel electrophoresis; growth factor; histochemistry /cytochemistry; hormone inhibitor; hormone regulation /control mechanism; mass spectrometry; progesterone; progestins; prostaglandin F; radioimmunoassay; radiotracer; sex hormones; steroid hormone biosynthesis; tissue /cell culture; ultracentrifugation

A technique to culture rabbit epithelial endometrial cells in chemically defined medium has been developed. Estrogens were found to promote cell division, whereas progesterone had an opposite effect. These cultured cells were found to be either noncycling (GO) or cycling. Both cell subpopulations were isolated, and it was found that the GO cells were the target of estrogens. Interaction between progesterone and the cycling cells was necessary to obtain an antagonistic effect on the estrogen action on the GO cells due to the production of a diffusible factor. A similar factor, probably a protein, appears to be produced by high density cultures that do not respond to estrogen stimulation. In the process of isolating this estrogen inhibitor factor, another one having estrogen-amplification effects was detected. It was also found that the cultured cells synthesize a glycoprotein called uteroglobin. Its production is regulated by estrogens and progesterone. Estradiol and progesterone decrease the number of estrogen receptors in cultures, apparently by different mechanisms of action. Cultured cells grown on floating collagen gels exhibit cycling growth kinetics. These cycles of cell proliferation and death are elicited by two diffusible factors made by the cells. These two factors inducing either cell death or cell proliferation, are apparently proteins. We will continue to study our experimental system by analyzing the mechanism of action of ovarian sex hormones in regulating cell proliferation, cell death, uteroglobin production, and hormone receptors, as well as isolating the factors regulating cell growth and estrogen effects. The endpoint of our research is to improve our comprehension of the mechanism by which sex hormones regulate proliferation and differentiation of endometrium. It\is expected that the study of our hormone-responsive system will help to advance the understanding of the etiology and pathogenesis of endometrial hyperplasia and carcinoma in particular and hormone-related cancer in general. (D)

化学培养兔子宫内膜上皮细胞的技术 已开发出定义介质。雌激素被发现能促进细胞 黄体酮则有相反的作用。这些有教养的 发现细胞不是非周期细胞(GO)，就是周期细胞。两个单元格 分离出亚群，发现GO细胞是 雌激素的靶标。孕酮与周期细胞的相互作用 对雌激素的作用产生拮抗作用是必要的 GO细胞由于产生了一种扩散因子。一种类似的 因子，可能是一种蛋白质，似乎是由高密度培养产生的。 对雌激素刺激没有反应的人。在分离的过程中 这种雌激素抑制因子，另一种具有雌激素放大作用的因子 检测到了效果。还发现，培养的细胞合成了 一种叫做子宫红蛋白的糖蛋白。它的生产受到 雌激素和黄体酮。雌二醇和黄体酮会减少 显然是通过不同的机制 行动。生长在漂浮胶原胶上的培养细胞表现出循环 生长动力学。这些细胞增殖和死亡的周期是由 由细胞产生的两个扩散因子。这两个因素导致 无论是细胞死亡还是细胞增殖，显然都是蛋白质。我们会 继续研究我们的实验系统，通过分析机制 卵巢性激素在调节细胞增殖、细胞分化中的作用 死亡，子宫红蛋白的产生，激素受体，以及分离 调节细胞生长的因素和雌激素的作用。的终点 我们的研究是为了提高我们对性行为机制的理解 激素调节子宫内膜的增殖和分化。是这样的 希望对我们荷尔蒙反应系统的研究将有助于 提高对子宫内膜的病因和发病机制的认识 增生性和癌，特别是与激素相关的癌症 将军。(D)