FETAL HEAT PRODUCTION AND TEMPERATURE REGULATION

在出生时，新生的羔羊对寒冷的反应是引起颤抖和 不颤抖的生热作用，使产热量增加三到五 收牌。然而，如果胚胎绵羊在子宫内冷却，反应是 最低限度。即使提供额外的氧气和儿茶酚胺 模拟分娩条件，反应保持静止。生热 只有在血管闭塞后，反应才会增加并接近新生儿水平。 脐带。 脊髓闭塞促进生热的方式尚不清楚。 一种可行的可能性是，一种可能源于胎盘的抑制剂， 在出生前抑制产热。去除后的生热作用 在儿茶酚胺升高的刺激下开始。我们有 考虑了几个拟议的抑制剂候选人，并已 设计了实验来测试它们每一个。假设如下 以下是： 1)胎盘来源的腺苷强效抑制脂肪分解。 子宫。去除胎盘可以开始产热。 2)循环中的二十烷类化合物，可能是PGE2，在张力上抑制 宫内生热。出生后浓度逐渐减少 让生热作用开始。 3)生长激素在出生前强效抑制产热作用。 再一次，浓度的降低允许生热。 为了检验这些假说，我们提出了一系列的研究。 长期准备、未麻醉的胎羊作为动物模型。 通过冷却羊水，在子宫内模拟分娩， 给胎儿肺部吸氧，然后夹住脐带。这个 将给出感兴趣的化合物和它们的对手。胎儿 反应将通过血浆甘油和游离脂肪的变化来评估 酸浓度，棕色脂肪温度的变化，以及特定的 放射性标记鸟苷二磷酸的结合，国内生产总值(一个指数 棕色脂肪中的解偶联蛋白质活性)。全身反应将是 以氧气消耗和核心体的测量为特征 温度。另一项工作将测试是否不颤抖 产热作用发生在棕色脂肪以外的组织中。特定组织 将使用血管活性物质和钙离子流量阻滞剂进行测试。 我们的目标是继续调查激活和 控制胎儿和新生绵羊的产热反应。这些 研究与新生儿体温过低的治疗直接相关。 人类，更广泛地说，是为了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.