NEUROPEPTIDE CONTROL OF THYROID SECRETION AND BLOOD FLOW

本项目源于校长最近的合作研究 提供免疫组织化学证据的调查员 甲状旁腺神经内的几种神经肽(NP‘s) 毛囊细胞和血管。该研究的目的是 描述某些NP对甲状腺激素分泌和 血流量，并研究它们之间的功能关系。这些 最近发现，NP存在于许多不同的组织中，它们 通常与肿瘤或疾病状态有关。然而，对 NP的功能重要性没有跟上更多的 对它们分布的描述性研究。这项研究计划包括 主要是体内实验，其中甲状腺激素分泌和 相同大鼠的血流量是通过放射免疫分析和一种 分别对放射性微球技术进行适配。这个 NP的主要兴趣是血管活性肠肽(VIP)，物质 P、神经肽Y和肽HI，但其他NP也将被检测。 将测试物质注入尾静脉、颈动脉或 局部应用于一个甲状腺叶。将对所有NP进行测试 与促甲状腺激素的相互作用对分泌和血流的影响。 内源性NP可能参与调节甲状腺分泌 和/或血流，将通过药物操纵来研究 内源性池，被动免疫，以及使用具有 甲状腺的VIP神经支配增加。在影响的NP的情况下 无论是分泌还是流动，都将尝试确定是否有 这些影响是他者的结果，而不是直接的 NP的影响。大多数体内实验将使用 麻醉的大鼠，但也有一些也将在未麻醉的动物身上完成 带着慢性血管导管。去垂体大鼠的实验研究 将进行以确定是否观察到的系统性影响 NP输注是由于直接的甲状腺影响或继发于对 脑下垂体促甲状腺激素分泌。最后，对于那些被发现影响 甲状腺在体内，将在体外使用甲状腺进行额外的研究。

This project emanates from recent collaborative studies by the Principal Investigator which provided immunohistochemical evidence for the presence of several neuropeptides (NP's) within thyroid nerves which innervate both follicle cells and blood vessels. The objectives of the study are to characterize the effects of certain NP's on thyroid hormone secretion and blood flow, and to study the functional relationship between these. These NP's have recently been found to occur in many different tissues and they are often associated with tumors or disease states. However, studies of the functional importance of the NP's have not kept pace with the more descriptive studies of their distribution. This research proposal consists primarily of in vivo experiments in which thyroid hormone secretion and blood flow are determined in the same rats by radiommunoassay and by an adaptation of the radioactive microsphere technique, respectively. The NP's of primary interest are vasoactive-intestinal peptide (VIP), substance P, neuropeptide Y, and peptide HI, but other NP's will also be tested. Test substances are to be administered into a tail vein, carotid artery, or topically applied to one thyroid lobe. All NP's will be tested for interactions with TSH regarding effects on both secretion and blood flow. The possible involvement of endogenous NP's in regulating thyroid secretion and/or blood flow, will be investigated by pharmacological manipulation of endogenous pools, passive immunization, and the use of an animal model with increased VIP innervation of the thyroid. In the case of NP's which affect both secretion and flow, attempts will be made to determine whether either of these effects is a result of the other, rather than being a direct effect of the NP. Most of the in vivo experiments will be performed using anesthetized rats, but some will also be done in unanesthetized animals with chronic vascular catheters. Experiments in hypophysectomized rats will be carried out to determine whether the observed effects of systemic NP infusions are due to direct thyroid effects or secondary to effects on pituitary TSH secretion. Finally, for those NP's found to affect the thyroid in vivo, additional studies will be done using thyroids in vitro.