Thyroid hormones affect cellular metabolism by binding to a nuclear receptor and altering DNA transcription. How the hormones cross the plasma membrane and are translocated to the nucleus to exert their effects has not been fully elucidated. During my fellowship at the NIH, we found evidence for a saturable, stereospecific, energy dependent transport of both T3 and T4 into a mouse neuroblastoma cell line, NB41A3, which has 5'-monodeiodinase activity. Since cerebral cortical neurons derive up to 80% of their nuclear bound T3 via intracellular deiodination of T4, these findings are of interest. This proposal to extend these observations and isolate and characterize the putative plasma membrane transporter will be performed at the Department of Physiology and Biophysics of Case Western Reserve University School of Medicine. This position, my first academic appointment, will be shared with the Department of Medicine. During my first year on faculty, my time will be devoted entirely to initiating the laboratory work outlined in this proposal followed in successive years with increasing clinical responsibilities at Cleveland Metropolitan General Hospital, a Case Western Reserve University affiliated hospital where I completed my residency including a year as chief in Internal Medicine and in Endocrinology and Metabolism. This award which would insure protected time to further my research training will help me develop into a independent investigator. Dr. Antonio Scarpa is the Chairman of the Department of Physiology and Biophysics and he is my scientific mentor. His laboratory is equipped to carry out the procedures proposed in particular the fluorescent imaging of rhodamine-labeled thyroid hormone cellular uptake and the probable intracellular calcium fluxes caused by interaction of thyroid hormone with the plasma membrane. He is a well respected researcher and teacher in whose laboratory I can broaden my research skills while investigating the transport of thyroid hormones across CNS plasma membranes.
