SELECTION OF THE DOMINANT FOLLICLE AND THE IGF SYSTEM

优势卵泡和 IGF 系统的选择

• 批准号: 6363441
• 负责人: JOANNE E. FORTUNE
• 金额: $ 19.1万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-10 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6363441
• 关键词: binding proteins; cow; endopeptidases; enzyme activity; gonadotropins; graafian follicles; granulosa cell; insulinlike growth factor; messenger RNA; natural selections; prostaglandin F; recombinant proteins; western blottings

What regulates the selection, from among a cohort, of a species-specific number of follicles for ovulation is one of the most important unanswered questions in mammalian ovarian biology. This proposal is focused on the potential role of the insulin-like growth factor (IGF) system in selection of follicles for dominance and potential ovulation. Cattle are an ideal model for such studies because ultrasound imaging has elucidated the regular patterns of follicular recruitment, selection, and dominance that occur at predictable intervals and can be manipulated experimentally. IGF is known to synergize with FSH to promote follicular growth and differentiation. In contrast, IGF binding proteins (IGFBPs) bind IGF and inhibit its actions within the follicle. IGFBP proteases release IGF from its BPs and allow it to act on follicular cells. Our preliminary data indicate that inhibitory IGFBPs are lower in dominant than in subordinate follicles and that dominant follicles acquire a protease for at least one of the IGFBPs (IGFBP-4) around the time of follicular selection for dominance. Therefore, the overall hypothesis of this proposal is that the ovarian IGF system plays a critical role in the selection of the dominant follicle in cattle. This hypothesis will be tested first by determining the relative levels of inhibitory IGFBPs (BP-4 and BP-2) and their putative proteases in follicular fluid and relative levels of IGFBPs and their mRNAs in follicular tissue from follicles obtained before, during and after follicular selection (Specific Aims 1 and 2). In Specific Aim 3 an experimental model for producing co-dominant follicles will be used to further test the postulated association between dominance and specific changes in IGFBPs and their proteases. Since waves of follicular development are believed to be initiated by small increases in plasma FSH, Specific Aim 4 is to determine the effects of gonadotropins on the secretion of IGFBPs and IGFBP protease activity by theca and granulosa cells isolated from follicles at specific times during follicular selection and cultured in vitro. Specific Aim 5 is to establish a causal link between changes in IGFBPs and their proteases and selection of the dominant follicle by determining if specific IGFBPs inhibit gonadotropin and/or IGF-I-induced steroid secretion by granulosa and theca cells in vitro.

从同类中，可以调节物种数量排卵的卵泡的选择是哺乳动物卵巢生物学中最重要的未解决问题之一。该建议的重点是胰岛素样生长因子（IGF）系统在选择卵泡以进行优势和潜在排卵中的潜在作用。 牛是此类研究的理想模型，因为超声成像已经阐明了以可预测的间隔发生的卵泡募集，选择和优势的规则模式，并且可以通过实验进行操作。 已知IGF与FSH协同作用，以促进卵泡生长和分化。 相反，IGF结合蛋白（IGFBP）结合IGF并抑制其在卵泡中的作用。 IGFBP蛋白酶从其BPS释放IGF，并使其作用于卵泡细胞。 我们的初步数据表明，抑制性IGFBP的显性抑制作用低于下属卵泡，并且显性卵泡在卵泡选择时至少为IGFBPS（IGFBP-4）中的至少一个IGFBP（IGFBP-4）获得蛋白酶。 因此，该提议的总体假设是卵巢IGF系统在牛中主要卵泡的选择中起着至关重要的作用。 该假设将首先通过确定抑制性IGFBP（BP-4和BP-2）的相对水平及其在卵泡液中的假定蛋白酶以及IGFBPS的相对水平及其在卵泡中获得的卵泡组织中的IGFBPS及其mRNA及其mRNA，在卵泡之前和之后获得的卵泡组织（特定的目标是1和2）。 在特定的目标3中，用于产生共同卵泡的实验模型将用于进一步测试IGFBPS及其蛋白酶的优势和特定变化之间的假定关联。 由于据信卵泡发育的波是由血浆FSH的少量增加引发的，因此特定的目的4是确定促性腺激素对theca和grolanulosa细胞的分泌IGFBPS和IGFBP蛋白酶活性在卵泡中选择和培养的培养时间的特定时间。具体目的5是通过确定特定的IGFBP是否抑制促性腺激素和/或IGF-I诱导的类固醇分泌的颗粒和theca细胞在体外，建立了IGFBPS及其蛋白酶的变化与其蛋白酶的选择与选择显性卵泡的选择之间的因果关系。