RAS Proto-Oncogene Function in Corpus Luteum Activity

9600915金匠 在维持任何生物物种方面，个体最重要的功能是繁殖。 事实上，任何脊椎动物有机体的所有器官系统的功能是维持生命，使生殖能够发生。 在所有的哺乳动物物种中，生殖的成功主要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。 排卵时，卵母细胞从卵巢中挤出，原先包围卵母细胞的细胞变成一种称为黄体的结构。黄体细胞分泌雌性类固醇激素，孕酮。 黄体在适当的时间内分泌适当数量的孕酮是成功繁殖所必需的。 如果循环孕酮水平太低，或者如果分泌适量的时间太短，受精卵母细胞的植入将不会发生，或者如果植入发生，妊娠将无法维持。 在非妊娠周期的情况下，如果孕酮水平过高，或分泌时间过长，则不会发生后续排卵。 因此，黄体分泌孕酮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孕酮正常分泌的血生激素物质作出反应。 目前，使黄体细胞对控制孕酮分泌的激素产生反应的特殊生化机制尚不清楚。 事实上，正是这些机制负责正常的黄体功能。 PI最近发现，在大鼠中，卵巢中含有的特定蛋白质K-ras p21蛋白质的量反映了黄体分泌孕酮的模式。 此外，当抗该蛋白质的抗体在体外掺入黄体细胞时，这些细胞的孕酮分泌显著减少，从而证明该蛋白质在黄体细胞的孕酮产生/分泌中起作用。 本研究的目的是确定K-ras p21蛋白影响黄体孕酮分泌的具体方式，并确定这种p21蛋白是否在黄体分泌其他激素中起作用。 K-ras p21蛋白存在于所有哺乳动物细胞中。 因此，拟议的研究结果将对理解卵巢激素分泌机制以及理解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。

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.