THE CONTROL OF GROWTH FACTORS

这些研究将确定生长激素释放的作用， 生长激素释放抑制因子 （SRIF）在控制生长激素（GH）分泌的 新生猴作为人类发育的模型。 恒河 猴子的内分泌特征与人类相似 并允许详细研究下内分泌相互作用 在道德上不可能达到的受控条件 在人类身上。 生长激素缺乏的灵长类动物模型 将允许诊断和治疗技术的研究 这可能对患有生长激素的儿童有益 缺乏症，除了生长不良， 严重的低血糖及其神经后遗症。 拟研究的事件序列为：（1）新生儿 灵长类动物血浆生长激素水平升高， 下丘脑-垂体轴，导致SRIF降低， GHRH比值;（2）出生后6天GH下降， 由于SRIF/GHRH比率的逐渐增加;（3）较低 新生儿血浆IGF I值高于成人， GH对IGF I产生的刺激不足，原因如下：a） GH分泌减少或B）GH受体数量不足。 研究将在长期患有 放置的静脉导管终止于皮下端口 （新生儿）或穿过保护性金属电缆 连接到笼子外面的旋转装置上（几个月大）。 然后，新生儿可以紧贴在椅子上， 双手被束缚，还有皮下组织。 因此，母亲和 孩子会在笼子里呆上几个小时。 的 几个月大的猴子可以在笼子里自由活动， 通过导管完成采样， 扰动 GHRH、SRIF和两者的抗血清（用于中和 GHRH或SRIF到达脑垂体受体之前）， 静脉推注或持续渗透压给药 微型泵和对血浆GH、SRIF、IGF I的影响 和IGF II测定。 这些研究旨在建立新生灵长类动物 模型作为一种有用的诊断和治疗测试方法 人类新生儿垂体机能减退症的治疗方案。 最终目标 是为了确定生长激素和生长调节素的生物作用， 人类胎儿和新生儿发育。

These studies will define the role of growth hormone releasing factor (GHRH) and growth hormone release inhibitory factor (SRIF) in the control of growth hormone (GH) secretion in the neonatal monkey as a model of human development. Rhesus monkeys have similar endocrine characteristics to human beings and allow the detailed study of endocrine interaction under controlled conditions which are ethically impossible to achieve in human beings. A primate model of growth hormone deficiency would allow study of diagnostic and therapeutic techniques which may be of benefit in children with growth hormone deficiency, a disease which can cause, besides poor growth, severe hypoglycemia and its neurological sequella. The proposed sequence of events to be studied are: (1) newborn primates have elevated plasma GH levels due to immaturity of the hypothalamic-pituitary axis, leading to a decreased SRIF to GHRH ratio; (2) the decrease in GH by 6 days after birth is due to a progressive increase in the SRIF/GHRH ratio; (3) lower plasma IGF I values in the newborn than in the adult are due to inadequate stimulation of IGF I production by GH due to a) decreased GH secretion or b) inadequate GH receptor number. Studies will be performed in animals that have chronically placed IV catheters terminating either in a subcutaneous port (newborns) or threaded through a protective metal cable attached to a swivel outside the cage (several months of age). The neonate can then cling to the chair adapted mother with hands restrained, and the subcultaneous. Thus, mother and child will spend all but a few hours in their cages. The several month old monkey can be free within its cage and sampling accomplished through the catheter without disturbance. GHRH, SRIF and antisera to both (to neutralize GHRH or SRIF before they reach pituitary receptors) will be given intravenously by bolus or continuously by osmotic minipumps and the resulting effects in plasma GH, SRIF, IGF I and IGF II determined. These studies are designed to establish the neonatal primate model as a useful method of testing diagnostic and therapeutic regimens for human neonatal hypopituitarism. The ultimate goal is to define the biological role of GH and the somatomedins in human fetal and neonatal development.