HYPOTHYROID AND AUTONOMIC CHANGES--ROLE OF MEDULLARY TRH

甲状腺功能减退症和自主神经变化——髓质 TRH 的作用

• 批准号: 2458903
• 负责人: HONG YANG
• 金额: $ 8.71万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-10 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458903
• 关键词: albino rat; autonomic nervous system; blood pressure; dorsal motor nucleus; efferent nerve; gastrins; gastrointestinal motility /pressure; gene expression; heart rate; hormone receptor; hormone regulation /control mechanism; hypothyroidism; in situ hybridization; medulla oblongata; neuroendocrine system; neurotransmitter transport; northern blottings; receptor expression; serotonin; serotonin receptor; somatostatin; thyroid hormones; thyroidectomy; thyrotropin releasing hormone; vagus nerve

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.

导致心动过缓，高血糖的中枢机制