PLURICRINE REGULATION OF FOLLICULAR TGF-B EXPRESSION

PLUCRINE 对滤泡 TGF-B 表达的调节

• 批准号: 3329985
• 负责人: JEFFREY V. MAY
• 金额: $ 10.77万
• 依托单位: UNIVERSITY OF KANSAS SCH OF MED WICHITA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3329985
• 关键词: animal tissue; autocrine; bioassay; cell differentiation; cell growth regulation; epidermal growth factor; follicle stimulating hormone; gene expression; granulosa cell; immunoprecipitation; insulinlike growth factor; luteinizing hormone; nucleic acid hybridization; paracrine; platelet derived growth factor; radiotracer; swine; transforming growth factors

The modern view of ovarian folliculogenesis recognizes the potential regulatory impact of endocrine, paracrine, and autocrine factors on this process. Recent interest has focused upon the roles of intraovarian growth factors in the regulation of follicle cell proliferation and differentiation. Of particular interest is transforming growth factor-beta (TGF-B) by nature of its multifunctional role with respect to cell proliferation and differentiation. It is hypothesized that TGF-B of theca cell origin regulates follicle development in the pig by regulation of granulosa and theca cell proliferation and differentiation. Theca cell TGF-B expression is in turn regulated by endocrine factors and intraovarian growth factors. This project will focus upon testing this hypothesis by analyzing the regulation of TGF-B production in porcine theca cells at four distinct levels: (A) secretion and (B) activation using a highly sensitive bioassay; (C) cellular accumulation using bioassay and by radiolabeled amino acid incorporation and immunoprecipitation; and (D) transcription, by analysis of TGF-B mRNA production using specific cDNA hybridization. With these as endpoints the following questions will be addressed: (1) Do theca cells produce TGF-B and if so what TGF-B subtype? (2) Do luteinizing hormone (LH) and/or follicle-stimulation hormone (FSH) directly regulate TGF-B production by the theca cells and at what level? (3) Do TGF-a/EGF, PDGF, IGF-I, and TGF-B, growth factors which regulate theca and granulosa cell proliferation and differentiation, directly regulate the production of theca cell TGF-B and at what level? (4) Do granulosa cells regulate the production of theca cell TGF-B? (5) Do LH, FSH, TGFa/EGF, PDGF, IGF-I and TGF-B act through granulosa cells to regulate theca cell TGF-B production? The studies outlined above and detailed herein will provide a comprehensive analysis of the regulation of expression and activation of a potent growth factor implicated in the regulation of follicle development. Moreover, they will provide a means with which to test statements with respect to the autocrine and paracrine roles of growth factors in follicle cell function.

卵巢卵泡发生的现代观点认为， 内分泌、旁分泌和自分泌因子对此的调节作用 过程 最近的兴趣集中在卵巢内生长的作用 调节卵泡细胞增殖的因子， 分化 特别令人感兴趣的是转化生长因子-β 由于TGF-β的多功能作用， 增殖和分化。 推测卵泡膜的TGF-β 细胞起源通过调节 颗粒细胞和卵泡膜细胞增殖和分化。 卵泡膜细胞 TGF-β的表达反过来又受内分泌因子的调节， 生长因子 本项目将侧重于测试这一假设， 分析猪卵泡膜细胞中TGF-β产生的调节， 不同的水平：（A）分泌和（B）使用高度敏感的 生物测定;（C）使用生物测定和放射性标记的细胞蓄积 氨基酸掺入和免疫沉淀;和（D）转录，通过 使用特异性cDNA杂交分析TGF-β mRNA的产生。 与 这些作为终点，将解决以下问题： (1)卵泡膜细胞是否产生TGF-B，如果是，TGF-B亚型是什么？ (2)促黄体生成激素（LH）和/或促卵泡激素（FSH） 直接调节卵泡膜细胞产生TGF-B，调节水平如何？ (3)TGF-α/EGF、PDGF、IGF-I和TGF-β，这些生长因子调节 卵泡膜和颗粒细胞增殖和分化，直接 调节卵泡膜细胞TGF-β的产生，在什么水平上？ (4)颗粒细胞调节卵泡膜细胞TGF-B的产生吗？ (5)LH、FSH、TGFa/EGF、PDGF、IGF-I和TGF-B是否通过颗粒细胞起作用 调节卵泡膜细胞TGF-B的产生 以上概述和本文详述的研究将提供一个全面的 分析一种有效的生长因子的表达和激活的调节 与卵泡发育调控有关的因子。 此外，委员会认为， 它们将提供一种手段， 生长因子在卵泡细胞功能中的自分泌和旁分泌作用。