The purpose of this project is to elucidate the functional interrelationships of the hypothalamic-pituitary thyroid axis, to elucidate the physiology of the various component hormones of this system (thyrotropin releasing hormone, thyro-tropin and the thyroid hormones) as regards their interactions with one another in health and disease, in man and animals, and to investigate the extrapituitary actions of thyrotropin releasing hormone. It is proposed: 1. To investigate further the mechanisms whereby thyrotropin releasing hormone and thyroid hormones interact to regulate thyrotropin secretion and to further delineatethe use of thyrotropin and thyroidal responses to thyrotropin releasing hormone as a clinical diagnostic tool. 2. To investigate the physiology of triiodothyronine and the regulation of the extrathyroidal formation of thyroid hormones. 3. To investigate the mechanisms of the synthesis and secretion of thyrotropin releasing hormone and the factors that regulate thyrotropin releasing hormone secretion, both in the hypothalamus and in extrahypothalamic neural sites. 4. To investigate the function of the thyrotropin releasing hormone found in extrahypothalamic tissue.