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

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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.