HYPOTHYROID AND AUTONOMIC CHANGES--ROLE OF MEDULLARY TRH

导致心动过缓、高血压病的中枢机制 压力、胃肠动力障碍和胃萎缩 甲状腺功能减退症的病因尚不清楚。最近的研究表明，TRH和 5-羟色胺(5-羟色胺)合成并共存于中缝髓核 支配脊交感神经和延髓迷走神经节前神经 运动神经元在中枢自主神经调节中起着重要作用。 本提案的假设是甲状腺激素调节 通过影响神经递质的合成和功能影响自主神经系统 TRH和5-羟色胺位于延髓中缝核。具体目标是： (1)探讨延髓TRH和5-羟色胺是否参与脑缺血再灌注损伤。 甲状腺功能减退症的自主神经障碍。迷走神经传出放电， 心率和血压、胃肠动力、胃窦 胃泌素和生长抑素基因的表达将在欧盟和 甲状腺功能减退大鼠。脑池内或鞘内注射和 延髓迷走神经运动核(DMN和AMB)内微量注射TRH 以及5-羟色胺或TRH抗体和特异性5-羟色胺受体拮抗剂 进行模拟或逆转观察到的自主神经紊乱 甲状腺功能减退。(2)甲状腺激素对TRH基因的调控作用 延髓中5-羟色胺的表达和5-羟色胺的转化以及c-fos的表达 中缝核团。Northern印迹和原位杂交检测TRH基因的表达 杂交、高效液相色谱检测5-羟色胺转化率及c-fos表达 免疫组织学将在甲状腺活动的条件下进行测量。这个 将观察时间进程和血浆甲状腺激素水平 与这些变化相关联。(3)研究其分布和分布。 延髓中缝核团中甲状腺激素受体的调节。一个 将使用基于聚合酶链式反应的分析来表征阿尔法 大鼠延髓β-甲状腺激素受体基因的表达。就地 将使用杂交的方法来定位受体基因的表达 不同条件下的甲状腺活动。 拟议中的研究将提供甲状腺激素可能起作用的证据。 直接作用于与自主神经功能有关的延髓核团 调节其神经肽的合成和周转 神经递质，并将提供有关机制的实质性信息 自主神经障碍通过哪些途径参与临床 甲状腺疾病的表现。

The central mechanisms responsible for the bradycardia, high blood pressure, gastrointestinal motility disorder, and gastric atrophy induced by hypothyroidism remains unknown. Recent studies revealed that TRH and serotonin (5-HT), synthesized and co-existing in medullary raphe nuclei and innervating spinal sympathetic and medullary vagal preganglionic motoneurons, play important roles in central autonomic regulation. The hypothesis of the present proposal is that thyroid hormone modulates the autonomic nervous system by influencing the synthesis and functions of TRH and 5-HT located in the medullary raphe nuclei. The specific aims are: (1) to evaluate whether medullary TRH and 5-HT are involved in the autonomic disorders in hypothyroidism. The vagal efferent discharges, heart rate and blood pressure, gastric and intestinal motility, antral gastrin and somatostatin gene expression will be measured in eu- and hypothyroid rats. Intracisternal or intrathecal injections and microinjection into the medullary vagal motonuclei (DMN and Amb) of TRH and 5-HT or TRH antibody and specific 5-HT receptor antagonists will be performed to imitate or to reverse the autonomic disorders observed in the hypothyroidism. (2) to demonstrate that thyroid hormones regulate TRH gene expression and 5-HT turnover as well as c-fos expression in the medullary raphe nuclei. TRH mRNA levels by Northern blot analysis and in situ hybridization, 5-HT turnover by HPLC and c-fos expression by immunohistology will be measured under conditions of thyroid activity. The time courses will be observed and the plasma thyroid hormone levels will be correlated with these changes. (3) to study the distribution and regulation of thyroid hormone receptors in the medullary raphe nuclei. A polymerase chain reaction based assay will be used to characterize alpha and beta thyroid hormone receptor mRNA expression in rat medulla. In situ hybridization will be used to locate the receptor gene expression under different conditions of thyroid activity. The proposed studies will provide evidence that thyroid hormone may act directly on the medullary nuclei related to autonomic function by regulating the synthesis and turnover of its neuropeptides and neurotransmitters and will yield substantive information on the mechanisms through which autonomic disorders participate in the clinical manifestations of thyroid diseases.