THYROID HORMONE REGULATION OF MOUSE SOMATOSTATIN TYPE 5

本研究的目的是为了更好地了解下丘脑-垂体-甲状腺轴和生长抑素能系统之间的相互作用以及它们对垂体促甲状腺激素调节的联合作用。使用小鼠TTT-97促甲状腺肿瘤模型，我们先前已经证明，甲状腺激素治疗与增强小鼠生长抑素受体5(Msst5)基因的表达有关，从而减小肿瘤大小。这些研究的目的是通过研究msst5基因的基本启动子活性及其受甲状腺激素的调节来描述这些体内观察。这些数据不仅将加深我们对生长抑素能系统和垂体调节的基本分子机制的了解，而且对于神经内分泌肿瘤的发病机制和治疗具有广泛的临床应用价值。生长抑素类似物奥曲肽已被用于治疗多种神经内分泌肿瘤，描述生长抑素能系统的分子机制将有助于这些疾病的临床应用。进一步了解生长抑素受体的功能和调节可能有助于开发更有效的生长抑素类似物来诊断和治疗神经内分泌肿瘤。拟议的研究将在科罗拉多大学健康科学中心内分泌科进行，科罗拉多大学健康科学中心在科罗拉多大学内分泌科主任E.C.Ridgway博士的指导下进行。首席研究员是一名内科博士后研究员，对基础科学研究和学术医学事业有着坚定的承诺。她的短期目标是完成这项提案中概述的研究，长期目标是成为一名训练有素的分子神经内分泌学领域的独立基础科学家。这项有指导的临床科学家发展奖(K08)将使她能够获得必要的技能，以在她作为独立研究员的发展中取得进步。该机构和她的导师为她作为一名内科科学家的成功提供了一个支持性的环境。

The goal of this research proposal is to gain a better understanding of the interaction between the hypothalamic- pituitary-thyroid axis and the somatostatinergic system and their combined effect of pituitary thyrotrope regulation. Using the murine TtT-97 thyrotropic tumor model, we have previously demonstrated that treatment with thyroid hormone reduces tumor size in association with enhanced expression of the mouse somatostatin receptor type 5 (msst5) gene. The studies proposed aim to characterize these in vivo observations by investigating basal promoter activity of the msst5 gene and its regulation by thyroid hormone. Not only will these data enhance our understanding of the basic molecular mechanisms of the somatostatinergic system and pituitary regulation, but have long range clinical applications regarding the pathogenesis and treatment of neuroendocrine tumors. The somatostatin analog, octreotide, has been used to treat a variety of neuroendocrine tumors and description of the molecular mechanisms of the somatostatinergic system will be of clinical application to these diseases. Further knowledge of somatostatin receptor function and regulation will potentially contribute to the development of more efficacious somatostatin analogs for the diagnosis and treatment of neuroendocrine tumors. The proposed research will take place in the Division of Endocrinology at the University of Colorado Health Sciences Center in Denver, CO under the direction of Division Chief Dr. E. C. Ridgway. The principal investigator is a physician postdoctoral fellow with a strong commitment to basic science research and a career in academic medicine. Her short term goal is to complete the studies outlined in this proposal and her long term goal is to become a well trained independent basic scientist in the field of molecular neuroendocrinology. This Mentored Clinical Scientist Development Award (K08) will enable her to gain the necessary skills required to progress in her development as an independent investigator. The institution and her mentors provide a supportive setting for her to flourish as a physician- scientist.