RAS Proto-oncogene Activity in Corpus Luteum Function

在所有哺乳动物物种中，繁殖成功与否 卵巢的正常功能。 正常的卵巢功能 目的，卵母细胞的生产，以及适当的生产， 分泌特定的类固醇和蛋白质激素。 哺乳动物 在卵巢中，卵母细胞被包裹在几层细胞中， 雌性类固醇激素雌激素。 在排卵期，卵母细胞 从卵巢和以前包围卵巢的细胞中挤出 卵母细胞变成一种叫做黄体的结构。 的 黄体细胞分泌雌性激素 类固醇激素孕酮 孕酮的分泌从 黄体在适当的时间内适量， 成功繁殖所必需的。 因此，孕酮分泌 来自黄体的激素是生殖的关键决定因素 成功 黄体细胞必须通过以下方式做出反应： 生化机制，血液中的激素物质，控制 孕酮的正常分泌。 特定的生化 这些机制允许黄体对那些激素做出反应， 控制孕酮分泌的方法目前尚不清楚。 实际上， 这些机制负责正常的黄体功能。 金匠博士最近发现，在大鼠中， 一个特殊的基因，K-ras基因，在同一时间大大增加 从黄体中分泌孕酮的时间是在其 最大. 此外，当针对所编码的蛋白质的抗体 通过这种基因被纳入体外黄体细胞，孕酮 这些细胞的分泌物显著减少，因此 这表明K-ras基因编码的蛋白质p21 蛋白质，在孕酮的产生/分泌中起作用， 黄体细胞 本提案的目的是确定 p21蛋白影响黄体孕酮的具体方式 分泌以及p21蛋白是否在 其他来自黄体的激素。 K-ras基因产物p21 蛋白质，存在于所有哺乳动物细胞中。 因此， 拟议的研究将对理解 卵巢激素分泌机制以及我们对 所有哺乳动物细胞对激素和生长的反应方式 因素

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.