ESTROGEN ACTION IN THE ENDOCERVIX

雌激素在子宫颈内膜中的作用

• 批准号: 3073319
• 负责人: Beverly S. Chilton
• 金额: $ 5.31万
• 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/3073319
• 关键词: autoradiography; carbohydrate biosynthesis; cell differentiation; cell growth regulation; cervix; diethylstilbestrol; electron microscopy; epithelium; estrogen receptors; estrogens; glycoproteins; glycosylation; glycosyltransferase; growth /development; hormone regulation /control mechanism; laboratory rabbit; newborn animals; ovariectomy; progesterone; protein biosynthesis

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.

该提案的最终目标是了解雌激素如何 调节不同宫颈内细胞的粘液糖蛋白生物合成 人口。 这种理解对于生育/不孕至关重要 子宫颈内膜的调节。 具体来说，我们想要的是 了解雌激素对两种限速酶的调节，即 N-乙酰氨基半乳糖：多肽转移酶，负责 粘蛋白型O-糖基化或新链合成的起始；和 N-乙酰氨基葡萄糖转移酶，一种参与延伸的酶 粘蛋白型寡糖。 这一目标将通过在最佳条件下测量酶活性来实现 成人宫颈上皮基质复合体的状况， 新生儿和己烯雌酚治疗的动物。 主要重点将 确定这些酶中的一种或两种的活性是否 雌激素依赖性和/或黄体酮拮抗。 三步走 方法将包括：1）测量潜在差异 超微结构不同的上皮细胞群中的酶活性 通过单位重力沉降分离。 激素依赖性变化 这些酶中的一种或两种的活性将在不同的条件下测量 宫颈内膜上皮细胞群，来自对比动物 荷尔蒙状态，即雌激素主导（发情）、黄体酮主导 （假孕 5 天）并切除卵巢，接受类固醇治疗。 2）使用 新生动物将可以确定是否获得 个体上皮细胞的雌激素受体先于雌激素受体出现 糖蛋白生物合成。 潜在的变化 N-乙酰氨基半乳糖：多肽转移酶或 N-乙酰氨基葡萄糖转移酶活性将用作标记物 雌激素在产后分化过程中的作用 合成糖蛋白的宫颈管上皮细胞群。 3）在 试图拓宽视野，早期致畸作用 己烯雌酚对宫颈内膜细胞组成的影响 上皮细胞将与其影响进行比较 N-乙酰氨基半乳糖：多肽转移酶和/或 N-乙酰氨基葡萄糖转移酶活性。