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LYSOSOMAL MECHANISMS OF BLASTOCYST IMPLANTATION

囊胚植入的溶酶体机制

基本信息

批准号：
3311376
负责人：
BRUCE C MOULTON
金额：
$ 11.97万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-09-01 至 1991-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3311376
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

项目摘要

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.

LN对卵巢分泌孕激素和雌激素的反应在怀孕早期，哺乳动物的子宫发育能力执行囊胚所需的复杂细胞活动植入。子宫腔上皮细胞维持宫腔内通过分泌和内吞作用为囊胚提供环境用于囊胚黏附的适当基质，以及似乎将信息从胚泡传递到下层基质启动蜕膜化。As植入在此过程中，腔上皮细胞在植入室和广泛的外周重建。这些细胞功能需要积极参与溶酶体和精确的荷尔蒙控制合成和溶酶体酶的区划。我们过去的研究已经显示黄体酮增加溶酶体组织蛋白酶D的活性以及腔上皮细胞中这种酶的合成速度。孕激素预处理后，雌二醇会改变这些细胞对蜕膜生成的刺激有反应。上皮细胞早孕期间的功能可能取决于溶酶体蛋白水解酶与细胞内的变化这些细胞内溶酶体的功能。为了澄清黄体酮和雌二醇调控的生化机制上皮细胞的酶含量和细胞内活性溶酶体，提出了以下具体目标：(1)改变在子宫活动中编码组织蛋白酶D的信使核糖核酸在孕激素和雌激素治疗后测量。(2)前体- 不同分子量形式之间的产品关系子宫组织蛋白酶D将被确立，从而使荷尔蒙可以确定组织蛋白酶D的加工和激活的控制。 (3)将鉴定组织蛋白酶D的糖基化形式，并它们糖基化的荷尔蒙控制决定了。(4)我们将检测蛋白质中组织蛋白酶D的细胞内功能退化。溶酶体酶调控的研究进展妊娠早期的合成和细胞内活动应提供进一步的生物化学机制的解释孕激素和雌激素控制上皮细胞功能子宫内膜对激素反应能力的发展植入胚泡。更好地理解细胞控制子宫内膜中的机制应该有助于我们的基本对怀孕早期的知识和对发展限制人口增长的手段。