PLURICRINE REGULATION OF FOLLICULAR TGF-B EXPRESSION

PLUCRINE 对滤泡 TGF-B 表达的调节

• 批准号: 3329984
• 负责人: JEFFREY V. MAY
• 金额: $ 11.12万
• 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/3329984
• 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识到潜力 内分泌，旁分泌和自分泌因素对此的监管影响 过程。 最近的兴趣集中在沃里安内增长的作用上 调节卵泡细胞增殖和 分化。 特别感兴趣的是改变生长因子-beta （TGF-B）从本质上，其多功能作用相对于细胞 增殖和分化。 假设theca的tgf-b 细胞来源调节猪的卵泡发育 颗粒和theca细胞增殖和分化。 theca细胞 TGF-B表达反过 增长因素。 该项目将着重于检验这一假设 分析四个猪theca细胞中TGF-B产生的调节 不同的水平：（a）分泌和（b）使用高度敏感的激活 生物测定； （c）使用生物测定和通过放射性标记的细胞积累 氨基酸掺入和免疫沉淀； （d）转录，由 使用特定的cDNA杂交分析TGF-B mRNA的产生。 和 这些作为终点，将解决以下问题： （1）theca细胞会产生TGF-B，如果是的，什么TGF-B亚型？ （2）做黄体激素（LH）和/或卵泡刺激激素（FSH） 直接通过theca细胞和哪个水平调节TGF-B产生？ （3）DO TGF-A/EGF，PDGF，IGF-I和TGF-B，调节生长因子 theca和颗粒细胞的增殖和分化，直接 调节theca细胞TGF-B的产生以及在哪个水平？ （4）颗粒细胞是否调节theca细胞TGF-B的产生？ （5）DO LH，FSH，TGFA/EGF，PDGF，IGF-I和TGF-B通过颗粒细胞起作用 调节theca细胞TGF-B产生？ 上面概述和详细的研究将提供全面的 分析表达调节和有效生长的激活 因子与卵泡发育的调节有关。 而且， 他们将提供一种用于测试语句的手段 生长因子在卵泡细胞功能中的自分泌和旁分泌作用。