RAS Proto-Oncogene Function in Corpus Luteum Activity

RAS 原癌基因在黄体活动中的功能

• 批准号: 9600915
• 负责人: Laura Goldsmith
• 金额: $ 21.3万
• 依托单位: Rutgers, The State University of New Jersey-RBHS-New Jersey Med
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-15 至 1999-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9600915&HistoricalAwards=false
• 关键词: RAS; Proto; Oncogene; Function; Corpus

9600915 Goldsmith The most important function of the individual in contributing to the maintenance of any biological species is reproduction. In fact, all organ systems of any vertebrate organism function to maintain life to enable reproduction to occur. In all mammalian species, reproductive success is critically dependent upon normal function of the ovary. Normal 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 ovulation, the oocyte is extruded from the ovary and the calls 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. If circulating progesterone levels are too low or if secretion of the proper amounts occurs for too short of a time period, implantation of the fertilized oocyte will not occur or if implantation does occur, the pregnancy will not be maintained. In the case of a nonpregnant cycle, if progesterone levels are too high, or secretion occurs for too long a time period, a subsequent ovulation will not occur. Thus, progesterone secretion from the corpus luteum is a critical determinant of reproductive success. The cells of the corpus luteum respond, through biochemical mechanisms, to blood born hormonal substances which control the normal secretion of progesterone. The specific biochemical mechanisms which allow the luteal cells 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. The PI has recently discovered that, in the rat, the amounts of a particular protein, the K-ras p21 protein, contained in the ovary mirror the pattern of secretion of progesterone from the corpus luteum. Furthermore, when an antibody against this protein was incorporated into luteal cells in vitro, progesterone secretion from these cells was significantly decreased, thus demonstrating that this 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 K-ras p21 protein affects luteal progesterone secretion and to determine whether this p21 protein plays a role in the secretion of other hormones from the corpus luteum. The K-ras 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 understanding of the ways in which all mammalian cells respond to hormones and growth factors.

[600915]戈德史密斯在维持任何生物物种的过程中，个体最重要的功能是繁殖。事实上，任何脊椎动物的所有器官系统都有维持生命的功能，从而使繁殖得以发生。在所有的哺乳动物物种中，生殖的成功与否在很大程度上取决于卵巢的正常功能。特殊类固醇和蛋白质激素的正常产生和分泌。在哺乳动物的卵巢中，卵母细胞被几层细胞包裹着，这些细胞分泌雌性类固醇激素雌激素。在排卵期，卵母细胞从卵巢中挤出，之前包围卵母细胞的细胞变成了一种叫做黄体的结构。黄体的细胞，黄体细胞，分泌雌性类固醇激素，黄体酮。黄体在适当的时间内分泌适量的黄体酮是成功繁殖所必需的。如果循环黄体酮水平过低，或者分泌量适当的时间过短，受精卵就不会着床，或者即使着床了，也不能维持妊娠。在非怀孕周期，如果黄体酮水平过高，或分泌时间过长，随后的排卵将不会发生。因此，黄体的黄体酮分泌是生殖成功的关键决定因素。黄体细胞通过生化机制，对控制正常孕酮分泌的血液激素物质作出反应。黄体细胞对控制黄体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，正是这些机制导致了正常的黄体功能。PI最近发现，在大鼠中，卵巢中含有的一种特殊蛋白质K-ras p21蛋白的数量反映了黄体中黄体酮的分泌模式。此外，在体外黄体细胞中加入抗该蛋白的抗体后，这些细胞的黄体酮分泌明显减少，从而表明该蛋白在黄体细胞产生/分泌黄体酮中起作用。本研究的目的是确定K-ras p21蛋白影响黄体黄体酮分泌的具体方式，并确定该p21蛋白是否在黄体其他激素的分泌中起作用。K-ras p21蛋白存在于所有哺乳动物细胞中。因此，所提出的研究结果将对了解卵巢激素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。