Characterization of the TGF-beta receptor system in bovine granulosa cells

牛颗粒细胞中 TGF-β 受体系统的表征

• 批准号: 89678-2008
• 负责人: Carrière, Paul
• 金额: $ 1.46万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=390730
• 关键词: Characterization; TGF; beta; receptor; system

Infertility in dairy cattle is a principal restraint on economic success in the industry. Abnormal follicle growth and anoestrus is one of the principal causes in declining fertility in high-yielding dairy cattle. To resolve this problem, more basic knowledge is required to understand the endocrine mechanisms that control growth of the ovarian follicle which is the structure that contains the oocyte. Estradiol production by the granulosa cells of the follicle wall is the key to ensure normal follicle development, and estradiol secretion involves complex interactions between circulating molecules and locally produced factors. Transforming growth factor-ß (TGF-ß) is an important factor produced by the follicle cells and is known to modulate estradiol secretion, ovarian function and fertility. In our previous and ongoing studies we have shown that TGF-ß1 is a multifunctional factor which inhibits FSH-stimulated estradiol secretion but stimulates the secretion of estradiol in basal conditions (i.e. in the absence of FSH). The overall objective of my research program is to determine the mechanism of action of TGF-ß on estradiol secretion in bovine granulosa cells. Cultured bovine granulosa cells will be used to characterize the TGF-ß ligand/receptor system. The first objective is to characterize the effects of key hormones (FSH, androstenedione, IGF and insulin) on the mRNA expression of TGF-ß receptors (ALK-5, TGF-ßRII and betaglycan). The second objective is to determine the signal transduction mechanism of TGF-ß receptors looking at 1) the effects of TGF-ß isoforms on the mRNA expression and activation of Smads and 2) the differential effects of TGF-ß1 on gene expression in both basal and FSH-stimulated conditions using bovine gene microarrays. The third objective is to characterize the receptor system of TGF-ß in bovine follicles of different sizes. The study of the TGF-ß receptor/ligand system in bovine follicles as proposed in this research program will provide the basis for future research examining the effects of nutrition and stress on estradiol secretion and follicle development to improve fertility in the bovine species.

奶牛不育是制约该行业经济成功的主要因素。卵泡发育异常和无情是高产奶牛生育力下降的主要原因之一。为了解决这个问题，需要更多的基础知识来了解控制卵泡生长的内分泌机制，卵泡是包含卵母细胞的结构。卵泡壁颗粒细胞产生雌二醇是保证卵泡正常发育的关键，而雌二醇的分泌涉及循环分子和局部产生因子之间复杂的相互作用。转化生长因子-ß （TGF-ß）是卵泡细胞产生的重要因子，已知可调节雌二醇分泌、卵巢功能和生育能力。在我们之前和正在进行的研究中，我们已经证明TGF-ß1是一种多功能因子，它抑制FSH刺激的雌二醇分泌，但在基础条件下（即没有FSH）刺激雌二醇分泌。我的研究计划的总体目标是确定TGF-ß对牛颗粒细胞分泌雌二醇的作用机制。培养的牛颗粒细胞将用于表征TGF-ß配体/受体系统。第一个目的是表征关键激素（FSH、雄烯二酮、IGF和胰岛素）对TGF-ß受体（ALK-5、TGF-ß rii和β多糖）mRNA表达的影响。第二个目标是确定TGF-ß受体的信号转导机制，研究1)TGF-ß亚型对Smads mRNA表达和激活的影响，以及2)TGF-ß ß对基础和fsh刺激条件下基因表达的差异影响。第三个目的是表征TGF-ß在不同大小的牛卵泡中的受体系统。本课题对牛卵泡中TGF-ß受体/配体系统的研究，将为进一步研究营养和应激对雌二醇分泌和卵泡发育的影响，从而提高牛的生育能力提供基础。