ESTROGEN ACTION IN THE ENDOCERVIX

雌激素在子宫颈内膜中的作用

• 批准号: 3073316
• 负责人: Beverly S. Chilton
• 金额: $ 5.12万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3073316
• 关键词: autoradiography; carbohydrate biosynthesis; cell differentiation; cell growth regulation; cervix; diethylstilbestrol; electron microscopy; epithelium; estrogens; glycosyltransferase; growth /development; hormone regulation /control mechanism; newborn animals; ovariectomy; progesterone

The ultimate objective of this proposal is to understand how estrogen regulates mucus glycoprotein biosynthesis in different endocervical cell populations. This understanding is critical to fertility/infertility regulation in the endocervix. Specifically what is desired is an understanding of estrogen regulation of two rate-limiting enzymes, namely, N-acetylgalactosaminyl:polypeptide transferase, the enzyme responsible for the initiation of mucin-type O-glycosylation or new chain synthesis; and N-acetyl glucosaminyltransferase, an enzyme involved in the elongation of mucin-type oligosaccharides. This goal will be achieved by measuring enzyme activities, under optimal conditions in the endocervical epitherlial-stromal complex of adult, neonatal and diethylstilbestrol-treated animals. The principal focus will be on determining if the activity of one or both of these enzymes is estrogen-dependent and/or progesterone-antagonized. The three-step approach will include: 1) the measurement of potential differences in enzyme activities in ultrastructurally distinct epithelial cell populations isolated by unit gravity sedimentation. Hormone dependent changes in the activity of one or both of these enzymes will be measured in different endocervical epithelial cell populations, from animals in contrasting hormonal states, i.e., estrogen-dominated (estrous), progesterone-dominated (5-day pseudopregnant) and ovariectomized, steroid treated. 2) Using neonatal animals it will be possible to determine if the acquisition of estrogen receptor by individual epithelial cells precedes the onset of glycoprotein biosynthesis. Potential changes in N-acetylgalactosaminyl:polypeptide transferase or N-acetylglucosaminyltransferase activities will be used as markers for estrogen action during postnatal differentiation of specific glycoprotein-synthesizing endocervical epithelial cell populations. 3) In an attempt to broaden the perspective, the early teratogenic effect of diethylstilbestrol on the cellular composition of the endocervical epithelium will be compared with its effect on N-aceytlgalactosaminyl:polypeptide transferase and or N-acetylglucosaminyltransferase activities.

该提议的最终目标是了解雌激素 调节不同宫颈细胞中粘液糖蛋白的生物合成 人群。 这种理解对于生育/不孕症至关重要 内部的调节。 特别是想要的是 了解两种限速酶的雌激素调节，即 N-乙酰基半乳糖胺：多肽转移酶，负责的酶 粘蛋白型O-糖基化或新链合成的启动；和 N-乙酰基葡萄糖氨基转移酶，一种参与伸长的酶 粘蛋白型寡糖。 该目标将通过在最佳的情况下测量酶活性来实现 成人宫颈内膜核菌群中的条件， 新生儿和二乙基甲虫治疗的动物。 主要重点将 确定一种或两种酶的活性是 雌激素依赖性和/或孕激素抗抑制剂。 三步 方法将包括：1）测量潜在差异 超微结构上不同上皮细胞种群中的酶活性 通过单位重力沉积分离。 激素依赖性变化 其中一种或两种酶的活性将在不同的 宫颈上皮细胞种群，来自动物的对比 激素状态，即以雌激素为主（雌激素），孕酮为主 （为期5天的假孕剂）和卵巢切除术，接受类固醇。 2）使用 新生动物可以确定是否获得 单个上皮细胞的雌激素受体先于 糖蛋白生物合成。 潜在的变化 N-乙酰乳糖胺基：多肽转移酶或 N-乙酰葡萄糖氨基转移酶活性将被用作标记 特异性的产后分化期间的雌激素作用 糖蛋白合成的肠道宫颈上皮细胞群体。 3）in 试图扩大观点的尝试，即早期的致畸作用 餐饮室的细胞组成上的二乙基stilbestrol 将上皮与其对 n- acyytlgalactosaminyl：多肽转移酶和OR N-乙酰葡萄糖氨基转移酶活性。