LYSOSOMAL MECHANISMS OF BLASTOCYST IMPLANTATION

囊胚植入的溶酶体机制

• 批准号: 3311375
• 负责人: BRUCE C MOULTON
• 金额: $ 11.75万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-09-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3311375
• 关键词: early embryonic stage; embryo implantation; endometrium; epithelium; estradiol; gel electrophoresis; glycosylation; hormone regulation /control mechanism; laboratory rat; lysosomes; messenger RNA; ovariectomy; peptidases; progesterone; progestins; protein biosynthesis; protein metabolism

ln response to the ovarian secretion of progesterone and estrogen during early pregnancy, the mammalian uterus develops the capacity to perform complex cellular activities required for blastocyst implantation. Luminal epithelial cells maintain the intrauterine environment of the blastocyst by secretion and endocytosis, provide an appropriate matrix for the adhesion of the blastocyst, and appear to transmit information from the blastocyst to the underlying stroma to initiate decidualization. As implantation proceeds, luminal epithelial cells undergo autolysis within the implantation chamber and extensive restructuring peripherally. These cellular functions require the active participation of lysosomes and precise hormonal control of the synthesis and compartmentalization of lysosomal enzymes. Our past studies have shown that progesterone increases lysosomal cathepsin D activity and rates of synthesis of this enzyme in luminal epithelial cells. Following progestin pretreatment, estradiol alters the capacity of these cells to respond to deciduogenic stimuli. Epithelial cell functions during early pregnancy may depend upon the content of lysosomal proteases as well as changes in the intracellular function of lysosomes within these cells. To elucidate the biochemical mechanisms by which progesterone and estradiol control the enzyme content and intracellular activity of epithelial lysosomes, the following specific aims are proposed: (1) Changes in the activity of uterine mRNA coding for cathepsin D will be measured after progestin and estrogen treatment. (2) Precursor- product relationships between the various molecular weight forms of uterine cathepsin D will be established so that the hormonal control of cathepsin D processing and activation can be determined. (3) The glycosylated forms of cathepsin D will be identified and the hormonal control of their glycosylation determined. (4) We will examine the intracellular function of cathepsin D in protein degradation. These studies of the control of lysosomal enzyme synthesis and intracellular activity during early pregnancy should provide further elucidation of the biochemical mechanisms by which progesterone and estrogen control epithelial function and the development of the endometrial capacity for response to the implanting blastocyst. Better understanding of cellular control mechanisms in the endometrium should contribute to our fundamental knowledge of the earliest stages of pregnancy and to the development of means by which to limit population growth.

响应卵巢分泌黄体酮和雌激素 在怀孕早期，哺乳动物的子宫发展出能力 执行囊胚所需的复杂细胞活动 植入。 管腔上皮细胞维持宫内 囊胚的环境通过分泌和内吞作用，提供 用于囊胚粘附的适当基质，以及 似乎将信息从囊胚传递到 底层基质启动蜕膜化。 作为植入 进行中，管腔上皮细胞在管腔内进行自溶 植入室和外围的广泛重组。 这些细胞功能需要细胞的积极参与 溶酶体和激素合成的精确控制 溶酶体酶的区室化。 我们过去的研究有 研究表明，黄体酮可增加溶酶体组织蛋白酶 D 的活性 以及该酶在管腔上皮细胞中的合成速率。 孕激素预处理后，雌二醇改变了 这些细胞对蜕膜刺激做出反应。 上皮细胞 怀孕早期的功能可能取决于 溶酶体蛋白酶以及细胞内的变化 这些细胞内溶酶体的功能。 为了阐明 黄体酮和雌二醇控制的生化机制 上皮细胞酶含量和细胞内活性 溶酶体，提出以下具体目标：（1）改变 编码组织蛋白酶 D 的子宫 mRNA 的活性将是 在孕激素和雌激素治疗后测量。 (2) 前体- 各种分子量形式之间的乘积关系 子宫组织蛋白酶 D 的建立将使得荷尔蒙 可以确定组织蛋白酶 D 加工和激活的控制。 (3) 组织蛋白酶 D 的糖基化形式将被鉴定并 确定了其糖基化的激素控制。 （4）我们 将检查蛋白质中组织蛋白酶 D 的细胞内功能 降解。 这些溶酶体酶控制的研究 妊娠早期的合成和细胞内活性应 进一步阐明其生化机制 黄体酮和雌激素控制上皮功能 子宫内膜反应能力的发展 植入囊胚。 更好地理解细胞控制 子宫内膜的机制应该有助于我们的基本 怀孕早期阶段的知识和 制定限制人口增长的手段。