THYROID HORMONE REGULATION OF MOUSE SOMATOSTATIN TYPE 5

本研究的目的是更好地了解下丘脑-垂体-甲状腺轴和生长抑素能系统之间的相互作用及其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，我们以前已经证明，甲状腺激素治疗与小鼠生长抑素受体5型（msst 5）基因的表达增强相关的肿瘤大小减少。 这些研究旨在通过研究msst 5基因的基础启动子活性及其受甲状腺激素的调节来表征这些体内观察结果。 这些数据不仅将增强我们对生长抑素能系统和垂体调节的基本分子机制的理解，而且对神经内分泌肿瘤的发病机制和治疗具有长期的临床应用。 生长抑素类似物奥曲肽已被用于治疗各种神经内分泌肿瘤，生长抑素能系统的分子机制的描述将在这些疾病的临床应用。 对生长抑素受体功能和调节的进一步了解将有助于开发更有效的生长抑素类似物用于神经内分泌肿瘤的诊断和治疗。这项研究将在科罗拉多州丹佛市的科罗拉多大学健康科学中心的内分泌科进行，由科主任E。C.里奇韦 主要研究者是一名医生博士后研究员，致力于基础科学研究和学术医学事业。 她的短期目标是完成本提案中概述的研究，长期目标是成为分子神经内分泌学领域训练有素的独立基础科学家。 这个指导临床科学家发展奖（K 08）将使她获得必要的技能，在她的发展作为一个独立的研究者。 该机构和她的导师为她提供了一个支持性的环境，使她成为一名医生-科学家。

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.