FETAL HEAT PRODUCTION AND TEMPERATURE REGULATION

刚出生的小羊羔对寒冷的反应是颤抖， 不颤抖产热，增加产热3到5- 折 然而，如果羊胎在子宫内被冷却， 最小的 即使提供额外的O2和儿茶酚胺， 模拟出生条件，反应保持静止。 产热 反应增加，只有在闭塞后才接近新生儿水平。 脐带 脐带阻塞促进产热的方式尚不清楚。 一个可行的可能性是，一种抑制剂，也许是胎盘来源的， 在出生前抑制产热。 当它被移除时， 在升高的儿茶酚胺刺激下开始。 我们有 考虑了提议的抑制剂的几种候选物， 设计实验来测试每一个。 假设如下 如下所示： 第一章 胎盘来源的腺苷紧张性抑制脂肪分解， 子宫。 胎盘的移除使产热开始。 （二） 循环中的类二十烷酸，可能是PGE2， 子宫内产热 出生后浓度下降 允许产热开始。 第三章 生长激素在出生前抑制产热。 同样，浓度的降低允许产热。 为了验证这些假设，提出了一系列研究， 长期制备的未麻醉的胎羊作为动物模型。 通过冷却羊水来模拟子宫内的分娩， 给胎儿的肺通氧气，然后勒住脐带 的 将给出感兴趣的化合物及其拮抗剂。 胎儿 将通过血浆甘油和游离脂肪酸的变化来评估反应。 酸浓度，棕色脂肪温度的变化，以及特定的 结合放射性标记的鸟苷二磷酸，GDP（一个指标， 棕色脂肪中的解偶联蛋白活性）。 全身反应将是 通过测量O2消耗和核心体 温度 另一项工作将测试不颤抖的人 产热发生在除棕色脂肪以外的组织中。 特定组织 将使用血管活性剂和Ca2+通量阻断剂进行测试。 我们的目标是继续研究激活和 控制胎儿和新生羊的产热反应。 这些 研究与新生儿体温过低的治疗直接相关 人类，更一般地，控制新陈代谢和生长。

At birth a newborn lamb responds to cold by inducing shivering and nonshivering thermogenesis, increasing heat production three- to five- fold. If a fetal sheep is cooled in utero, however, the response is minimal. Even if additional O2 and catecholamines are provided to simulate birth conditions, the response remains quiescent. Thermogenic responses increase and approach newborn levels only after occlusion of the umbilical cord. The means by which cord occlusion facilitates thermogenesis is unknown. One viable possibility is that an inhibitor, perhaps of placental origin, suppresses thermogenesis before birth. Upon its removal thermogenesis begins under the stimulation of elevated catecholamines. We have considered several candidates for the proposed inhibitor and have designed experiments to test each of them. The hypotheses are as follows: 1) Adenosine of placental origin tonically inhibits lipolysis in utero. Removal of the placenta allows thermogenesis to begin. 2) A circulating eicosanoid, possibly PGE2, tonically suppresses thermogenesis in utero. Diminishing concentrations after birth allow thermogenesis to begin. 3) Growth hormone tonically suppresses thermogenesis before birth. Again, diminishing concentrations allow thermogenesis. To test these hypotheses a series of studies are proposed using the chronically-prepared, unanesthetized fetal sheep as an animal model. Birth will be simulated in utero by cooling the amniotic fluid, ventilating the fetal lungs with O2, and snaring the umbilical cord. The compounds of interest and their antagonists will be given. Fetal responses will be assessed by changes in plasma glycerol and free fatty acid concentration, changes in brown fat temperature, and specific binding of radiolabeled guanosine diphosphate, GDP (an index of uncoupling protein activity in brown fat). Whole-body responses will be characterized by measurements of O2 consumption and core body temperature. An additional line of work will test whether nonshivering thermogenesis occurs in tissues other than brown fat. Specific tissues will be tested using vasoactive agents and blockers of Ca2+ flux. Our goal is to continue to investigate the signals that activate and control thermogenic responses in the fetal and newborn sheep. These studies are directly relevant to treatment of hypothermia in the newborn human and, more generally, to the control of metabolism and growth.