Functional roles of the relaxin ligand-receptor system in the thyroid

该计划解决了内分泌配体-受体作用和结构-功能细胞反应之间的基本关系。该研究计划旨在表征肽激素松弛素（RLN）作为细胞骨架和相关系统的新型形态功能调节剂的作用，导致甲状腺细胞中细胞运动和细胞极性的改变。我们已经确定甲状腺是喉返神经的靶器官。在我们的甲状腺细胞模型中，RLN增强细胞运动，改变囊泡运输，并通过增加弹性蛋白溶解细胞活性影响细胞外基质（ECM）降解。在目前的建议，我们将研究的分子网络，促进RLN诱导和LGR 7松弛素受体介导的细胞运动的变化。此外，我们还将研究松弛素对极化猪甲状腺细胞骨架丝的作用，并确定松弛素对极化猪甲状腺细胞囊泡运输的影响。最后，我将建立一个新的转基因小鼠模型与甲状腺球蛋白指导，甲状腺特异性过表达的LGR 7研究LGR 7刺激对甲状腺功能的影响在体内。这些结果对我们理解RLN的细胞功能具有重要意义，并为人类和动物细胞生物学中这种肽激素配体-受体系统的新特性提供了独特的见解。

The proposed program addresses a fundamental relationship between endocrine ligand-receptor action and structure-function cellular responses. This research program is aimed at characterizing the role of the peptide hormone relaxin (RLN) as a novel morpho-functional regulator of cytoskeletal and associated systems leading to alterations in cell movement and cell polarity in thyroid cells. We have identified the thyroid gland as a RLN target organ. In our thyroid cell models, RLN enhances cell movement, alters vesicular trafficking, and affects extracellular matrix (ECM) degradation by increasing elastinolytic cellular activity. In the present proposal we will study the molecular network which facilitates RLN-induced and LGR7 relaxin receptor-mediated changes in cell movement. Furthermore, we will study the role of relaxin on cytoskeletal filaments in polarized porcine thyroid cells and determine the effects relaxin elicits on vesicular transport in polarized porcine thyrocytes. Finally, I will create a novel transgenic mouse model with thyroglobulin-directed, thyroid-specific overexpression of LGR7 to study the effect of LGR7 stimulation on thyroid functions in-vivo. These results have significant implications for our understanding of the cellular functions of RLN and provide a unique insight into novel properties of this peptide hormone ligand-receptor system in human and animal cell biology alike.