Novel Insights into the Molecular Mechanisms of Human Thyrotropin Action: Structural, Physiological, and Therapeutic Implications for the Glycoprotein Hormone Family

I. Introduction A. Historical background B. TSH and the glycoprotein hormone family II. Structure-Function Relationships of TSH in Relation to Studies on Gonadotropins A. Methodological considerations B. Structure-function studies of protein domains C. Structure-function studies of carbohydrate chains III. Current Understanding of TSH/Glycoprotein Hormone Action A. Structural considerations B. Hormone-receptor interaction C. Cooperation of individual hTSH domains in receptor activation IV. Physiological and Pathophysiological Implications A. Carbohydrate heterogeneity B. Naturally occurring glycoprotein hormone mutations C. “Specificity spillover” syndromes V. Evolutionary Considerations A. Glycoprotein hormone specificity B. Evolutionary changes in TSH activity VI. Strategies in the Design of Novel TSH Analogs and Therapeutic Implications A. Clinical use of rhTSH B. Design of novel glycoprotein hormone analogs VII. Nonclassic Actions of TSH and Gonadotropins A. Extrathyroidal/extragonadal glycoprotein ho...