GROWTH HORMONE AND DIFFERENTIATION

本研究的目的是阐明S的发病机制。 人生长激素诱导小鼠3T3-F442a分化 成纤维细胞分化为终末分化的脂肪细胞。我们的工作 假设脂肪分化是一种多步骤的多激素 每一步都受生长激素和其他激素调节的过程 多肽激素。在这个假设中，我们认为GH素数 胰岛素和胰岛素样生长因子-1后续作用的细胞。 我们的初步数据表明，生长激素启动状态的签名是 细胞形态的变化，细胞骨架蛋白的变化 表达、大分子合成、抗有丝分裂和酪氨酸 特异的蛋白质磷酸化。荷尔蒙的确切顺序 调控步骤将通过分离细胞变种来阐明 具有独特的激素要求，使用悬浮培养和 识别特定的荷尔蒙反应。其作用机制是 将通过以下方式寻求分化和生长的生物反应 转录、蛋白质合成和蛋白质研究 磷酸化。将特别关注具体的 受特定荷尔蒙调节的蛋白质。初步 实验表明，生长激素调节磷酸化。 生长因子反应显著的蛋白质中的酪氨酸 感受器。将特别关注胰岛素，胰岛素 像生长因子-1，表皮生长因子，转化生长 因子-β和血小板衍生生长因子受体。这些研究 应该有助于理解增长的机制 荷尔蒙和其他荷尔蒙调节分化和生长。

The goal of this research is to elucidate the mechanism(s) by which human growth (hGH) induces differentiation to murine 3T3-F442A fibroblasts to terminally differentiated adipocytes. our working hypothesis is that adipose differentiation is a nultistep multihormone process in which each step is hormonally regulated by GH and other polypeptide hormones. In this hypothesis we suggest that GH primes cells for subsequent action by insulin and insulin-like growth factor-1. Our preliminary data suggest that signatures of the GH primed state are changes in cell morphology, altered patterns of cytoskeletal protein expression, macromolecular synthesis, anti-mitogenesis, and tyrosine specific protein phosphorylation. The exact sequence of hormonal regulatory steps will be elucidated by the isolation of cell variants with unique hormonal requirements, use of suspension culture and identification of specific hormonal responses. The mechanism of the biological responses of differentiation and growth will be sought by studies of transcription, protein synthesis, and protein phosphorylation. Particular attention will be directed to specific proteins which are regulated by specific hormones. Preliminary experiments suggest that growth hormone modulates phosphorylation of tyrosine in proteins with prominent responses in growth factor receptors. Particular attention will be directed to insulin, insulin like growth factor-1, epidermal growth factor, transforming growth factor-beta and platelet derived growth factor receptors. These studies should contribute to an understanding of the mechanism by which growth hormone and other hormones modulate differentiation and growth.