RAS Proto-oncogene Activity in Corpus Luteum Function

RAS原癌基因活性对黄体功能的影响

• 批准号: 9002110
• 负责人: Laura Goldsmith
• 金额: $ 5.4万
• 依托单位: New Jersey Medical School
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-15 至 1992-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9002110&HistoricalAwards=false
• 关键词: RAS; Proto; oncogene; Activity; Corpus

In all mammalian species, reproductive success is critically dependant upon normal function of the ovary. Normal ovarian function serves two purposes, production of the oocyte, and appropriate production and secretion of specific steroid and protein hormones. In the mammalian ovary, the oocyte is encased in several layers of cells which secrete the female sex steroid hormone estrogen. At ovualation, the oocyte is extruded from the ovary and the cells which previously surrounded the oocyte are changed into a structure called the corpus luteum. The cells of the corpus luteum, the luteal cells, secrete the female sex steroid hormone, progesterone. The secretion of progesterone from the corpus luteum in the proper amounts for the proper time period is required for successful reproduction. Thus, progesterone secretion from the corpus luteum is a critical determinant of reproductive success. The cells of the corpus luteum must respond, through biochemical mechanisms, to blood born hormonal substances which control the normal secretion of progesterone. The specific biochemical mechanisms which allow the luteal to respond to those hormones which control progesterone secretion are at present unknown. It is, in fact, these mechanisms that are responsible for normal luteal function. Dr. Goldsmith has recently discovered that, in the rat, the expression of a particular gene, the K-ras gene, increases greatly at the same time that the seretion of progesterone from the corpus luteum is at its maximum. Furthermore, when an antibody against the protein coded for by this gene was incorporated into luteal cells in vitro, progesterone secretion from these cells was significantly decreased, thus demonstrating that the protein encoded by the K-ras gene, the p21 protein, plays a role in the production/secretion of progesterone by the luteal cell. It is the objective of this proposal to determine the specific way in which the p21 protein affects luteal progesterone secretion and whether the p21 protein plays a role in the secretion of other hormones from the corpus luteum. The K-ras gene product, the p21 protein, is present in all mammalian cells. Thus, the results of the proposed studies will have a significant impact upon the understanding of ovarian hormone secretory mechanisms as well as our understanding of the ways in which all mammalian cells respond to hormones and growth factors.

在所有哺乳动物物种中，生殖成功关键依赖于卵巢的正常功能。正常的卵巢功能有两个目的，一是产生卵母细胞，二是产生和分泌特定的类固醇和蛋白质激素。在哺乳动物的卵巢中，卵母细胞被包裹在几层细胞中，这些细胞分泌雌性类固醇激素雌激素。在排卵时，卵母细胞从卵巢中挤出，以前围绕卵母细胞的细胞变成一种叫做黄体的结构。黄体细胞，黄体细胞，分泌女性性激素黄体酮。黄体分泌适量、适量的黄体酮是生殖成功的必要条件。因此，黄体分泌的孕酮是生殖成功的关键决定因素。黄体细胞必须通过生化机制对血液中控制孕酮正常分泌的激素物质做出反应。黄体对那些控制孕酮分泌的激素作出反应的具体生化机制目前尚不清楚。事实上，正是这些机制负责正常的黄体功能。戈德史密斯博士最近发现，在大鼠体内，一种特殊的基因K-ras基因的表达大大增加，同时黄体中的孕酮含量达到最大。此外，当针对该基因编码的蛋白的抗体在体外导入黄体细胞时，这些细胞的孕酮分泌量显著减少，从而表明K-ras基因编码的蛋白p21蛋白在黄体细胞产生/分泌孕酮方面起作用。这项建议的目的是确定p21蛋白影响黄体孕酮分泌的具体方式，以及p21蛋白是否在黄体分泌其他激素方面发挥作用。K-ras基因产物p21蛋白存在于所有哺乳动物细胞中。因此，这些研究的结果将对了解卵巢激素的分泌机制以及所有哺乳动物细胞对激素和生长因子的反应方式产生重大影响。