HORMONAL CONTROL OF GROWTH

荷尔蒙对生长的控制

• 批准号: 3312745
• 负责人: CHARLES S NICOLL
• 金额: $ 18.6万
• 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/3312745
• 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; insulinlike growth 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.

我们建议进行的研究的目的，是要取得一个更 完全了解激素和（GF）如何发挥作用， 调节大鼠不同阶段的生长和分化 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 从胚胎期到幼年期随发育而变化，或 亚成年期 一个相关假设的方面， (Sm)假设，也将进行评估。 这项研究将 可以放在4个相关领域进行：1.调控 胚胎和胎儿组织在体内的生长和分化 被GF和荷尔蒙所控制 2. 控制软骨的生长， 幼龄（即月龄）大鼠后肢肌肉， 荷尔蒙和GF。 3.调节肝脏分泌胰岛素- 比如生长因子I（IGF-I）。 4.变化分析 组织对激素或GF的依赖性或反应性， 发生在婴儿（即6天大）和 大鼠的青春期。 其中前3个领域将涉及慢性输注 将激素、GF或GF的抗血清注射到血管中， 连接到渗透微型泵的导管。 的实验 控制胚胎和胎儿组织的生长将涉及 双侧移植10天大鼠胚胎或15天胎儿 在幼年或成年大鼠的肾包膜下的爪 同一个近亲繁殖的品种 GF、激素和抗血清对 GFs对这些胚胎的生长和分化的影响将 通过将其注入右肾动脉进行研究。 激素和生长因子对软骨生长的影响， 肌肉将通过将它们注入到正确的共同 髂动脉（向一侧后肢供血）， 垂体切除（Hx）月龄大鼠。 GF抗体 将被注入同一动脉的快速增长的大鼠的 同龄。 激素（胰岛素、GH、T4和 皮质酮）对体内肝脏分泌IGF-I的影响将是 通过将它们注入Hx的肝门静脉来确定 大鼠 将通过测量血清IGF-I水平评估效应， 尾部生长和胫骨骺板宽度。 差异 激素依赖性和对生长的反应性， 将分析30日龄和30日龄的大鼠。 的时间变化 血清IGF-I水平（以及可能的其他生长因子）将 Hx后测量以及GH和T4对血清水平的影响 将测定胰岛素、IGF-I和GF。 的可能性 乳汁中的激素和生长因子支持乳鼠幼仔的生长， 也被研究。