Extrapituitary effects of somatostatins on growth

生物体生长的协调涉及许多外部和内部信号的整合，这些信号导致大量激素和生长因子的产生，包括生长激素(GH)和胰岛素样生长因子-I(IGF-I)。对各种线索是如何整合的，以及激素如何相互作用调节生长的理解还远远没有完成。在本项目中，将以虹鲑鱼为模式生物来评估生长抑素(SSS)对生长控制网络的影响。生长抑素是一种多功能的多肽激素家族。研究将揭示SSS对选定细胞类型(例如肝脏)的生长激素反应性的影响。这将涉及生长激素受体(GHR)的特性和SSS对GHR表达的影响的分析。研究还将阐明SSS对IGF-I合成和分泌的影响。此外，将确定SS对选定细胞类型(例如肌肉)中IGF-I反应性的影响。这将涉及IGF-I结合特性和IGF-I受体表达的分析。最后，SS的作用机制将通过确定SSS运行的信号通路和确定哪种SS受体亚型激活哪条信号通路来表征。该项目的成果将促进我们对正常生长控制过程的理解，并将应用于提高鱼类(例如水产养殖)、家禽和家畜的生长效率的努力，以及检测和治疗动物和人类的生长障碍。此外，该项目将扩大北达科他州的关键研究基础设施，使美国的科学事业多样化，并为本科生和研究生提供研究教育和培训机会，包括代表人数不足的群体的成员。

The coordination of organismal growth involves the integration of many external and internal cues that result in the production of numerous hormones and growth factors, including growth hormone (GH) and insulin-like growth factor-I (IGF-I). An understanding of how the various cues are integrated and how the interplay of hormones modulate growth is far from complete. In this project, rainbow trout will be used as a model organism to evaluate the effects of somatostatins (SSs), a multi-functional family of peptide hormones, on the growth control network. Research will reveal the influence of SSs on GH responsiveness in selected cell types (e.g., liver). This will involve the characterization of GH receptors (GHR) and an analysis of the effects of SSs on GHR expression. Research also will elucidate the influence of SSs on IGF-I synthesis and secretion. In addition, the effects of SS on IGF-I responsiveness in selected cell types (e.g., muscle) will be determined. This will involve an analysis of IGF-I binding characteristics and of IGF-I receptor expression. Lastly, the mechanisms of SS action will be characterized by identifying signal pathways through which SSs operate and by establishing which SS receptor subtype activates which signal pathway. The results of this project will advance our understanding of normal growth control processes and have application to efforts to improve growth efficiency of fish (e.g., aquaculture), poultry and domestic livestock, as well as to the detection and treatment of growth disorders in animals and humans. In addition, the project will expand critical research infrastructure in North Dakota, serving to diversify the nation's scientific enterprise, and afford research education and training opportunities to undergraduate and graduate students, including members of underrepresented groups.