HORMONAL CONTROL OF GROWTH

荷尔蒙对生长的控制

• 批准号: 3312744
• 负责人: CHARLES S NICOLL
• 金额: $ 18.01万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3312744
• 关键词: cartilage development; cell differentiation; corticosterone; embryo /fetus; embryo /fetus transplantation; growth /development; growth factor; hormone regulation /control mechanism; hypophysectomy; insulin; insulinlike factor; juvenile animal; laboratory rat; liver metabolism; mature animal; newborn animals; radioassay; thyroid hormones; thyroidectomy; thyroxine; tissue /cell culture

The objective of our proposed studies is to obtain a more complete understanding of how hormones and (GFs) function to regulate growth and differentiation of rats in different stages of their development. The major hypothesis being tested is that the dependence on and responsiveness to hormones and growth factors change with development from the embryonic to the juvenile or subadult period. Aspects of a related postulate, the somatomedin (Sm) hypothesis, will also be evaluated. The research to be conducted can be placed in 4 related areas: 1. Regulation of the growth and differentiation of embryonic and fetal tissues in vivo by GFs and hormones. 2. Control of growth of cartilage and muscle in the hindlimb of juvenile (i.e. month old) rats by hormones and GFs. 3. Regulation of hepatic secretion of insulin- like growth factor-I (IGF-I). 4. Analysis of the changing dependence or responsiveness of tissues on hormones or GFs that occurs during development between the infant (i.e. 6 day old) and juvenile periods in the rat. The first 3 of these areas will involve chronic infusion of hormones, GFs or antisera to GFs into blood vessels using catheters attached to osmotic minipumps. The experiments on control of growth of embryos and fetal tissues will involve bilateral transplantation of 10 day rat embryos or 15 day fetal paws under the kidney capsule of juvenile or adult rats of the same inbred strain. The effects of GFs, hormones and antisera to the GFs on the growth and differentiation of these embryos will be studied by infusing them into the right renal artery. The effects of hormones and GFs on growth of cartilage and muscle will be determined by infusing them into the right common iliac artery (which supples blood to one hindlimb) of hypophysectomized (Hx) month old rats. Antibodies to the GFs will be infused in the same artery of rapidly growing rats of the same age. The direct effects of hormones (insulin, GH, T4 and corticosterone) on hepatic secretion of IGF-I in vivo will be determined by infusing them into the hepatic portal vein of Hx rats. Effects will be assessed by measuring serum IGF-I levels, tail growth and width of the tibial epiphyseal plate. Differences in hormonal dependence and responsiveness for growth between 6 day and 30 day old rats will be analyzed. Temporal changes in serum IGF-I levels (and possibly other growth factors) will be measured after Hx and the effects of GH and T4 on serum levels of insulin, IGF-I and GFs will be determined. The possibility that hormones and GFs in milk support growth of suckling rat pups will also be studied.

我们建议的研究的目标是获得更多的 完全了解激素和(GFS)是如何发挥作用的 调节不同发育阶段大鼠的生长分化 他们的发展。正在测试的主要假设是 对激素和生长因子的依赖和反应性 从胚胎到幼年的发展变化或 亚成人期。一个相关假设的方面，即躯体原子化 (SM)假设，也将进行评估。未来的研究将是 可放在4个相关领域进行：1.监管 胚胎和胎儿组织在体内的生长和分化 由GFS和荷尔蒙引起。2.控制软骨的生长和 幼年(即一个月龄)大鼠后肢肌肉 荷尔蒙和GFS。3.调节肝脏胰岛素分泌- 如生长因子-I(IGF-I)。4.变化的原因分析 组织对激素或GFS的依赖性或反应性 发生在婴儿(即6天大的婴儿)和 在大鼠的幼年期。 这些领域中的前三个领域将涉及慢性输注 使用激素、GFS或抗GFS血清进入血管 附在渗透性小泵上的导管。的实验。 控制胚胎和胎儿组织的生长将涉及 10天大鼠胚胎或15天胎鼠双侧移植 幼年和成年大鼠肾被膜下足爪的实验研究 同样的近亲繁殖品系。GFS、激素和抗血清对小鼠肾功能的影响 GFS对这些胚胎的生长和分化的影响 通过将它们注入右肾动脉进行研究。 激素和GFS对软骨细胞生长和生长的影响 肌肉将通过将它们注入到右侧共同的 髂动脉(为一侧后肢供血) 去垂体(HX)月龄大鼠。针对GFS的抗体 将被注入快速生长的大鼠的同一条动脉 年龄相仿。激素(胰岛素、生长激素、T4和 皮质酮)体内对肝脏分泌IGF-I的影响 通过将它们注入HX的肝门静脉来确定 老鼠。将通过测量血清IGF-I水平来评估效果， 尾部生长和胫骨骨骺板的宽度。差异 6岁之间的激素依赖性和对生长的反应性 对日龄和30日龄大鼠进行分析。时间上的变化 血清IGF-I水平(可能还有其他生长因子) HX后测定及GH和T4对血清水平的影响 将测定胰岛素、IGF-I和GFS的水平。有没有可能 乳汁中的激素和GFS支持哺乳大鼠仔鼠的生长 也有待研究。