1 Introduction to G-Protein-Coupled Signal Transduction and Human Disease.- 2 Albright Hereditary Osteodystrophy, Pseudohypopara-thyroidism, and Gs Deficiency.- 3 Gas-Activating Mutations: A Cause of Acromegaly, Thyroid Adenomas, Fibrous Dysplasia, and the McCune-Albright Syndrome.- 4 Ulcerative Colitis in Mice Lacking G?i2.- 5 G Proteins Regulating Insulin Action and Obesity: Analysis by Conditional, Targeted Expression of Antisense RNA in vivo.- 6 G;12- and G?3- Subunits of Heterotrimeric G Proteins : A Novel Family of Oncogenes.- 7 Hypo- and Hyperthyroidism Caused by Mutations of the TSH Receptor.- 8 Disorders Caused by Mutations of the Lutropin/ Choriogonadotropin Receptor Gene.- 9 Inactivating and Activating Mutations of the FSH Receptor Gene.- 10 Nephrogenic Diabetes Insipidus and Vasopressin Receptor Mutations.- 11 Disorders with Increased or Decreased Responsiveness to Extracellular Ca2+ Owing to Mutations in the Ca2+0-Sensing Receptor.- 12 Constitutively Active PTH/PTHrP Receptors Cause Jansen's Metaphyseal Chondrodysplasia.- 13 Mutation of the Growth Hormone-Releasing Hormone Receptor in the little Mouse.- 14 Functional Variants of the MSH Receptor (MC1-R), Agouti, and Their Effects on Mammalian Pigmentation.- 15 ACTH Resistance Syndromes.- 16 Altering Adrenergic Signaling and Cardiac Function in Transgenic Mice.- 17 Dopamine Receptors in Human Disease: Lessons from Targeted Mouse Mutants.- 18 The ?3-Adrenergic Receptor and Susceptibility to Obesity, the Insulin Resistance Syndrome, and Noninsulin-Dependent Diabetes Mellitus.

Klappentext

"Theoretically, one should obtain essentially the same clinical picture from failure of an end-organ to respond to a hormone as from a decreased production or absence of said hormone. " With these words, Fuller Albright began his now classic paper describing a novel disease, pseudo hypoparathyroidism (PHP), and a novel concept, hormone resis­ tance as a cause of disease. Soon, other hormone resistance disorders such as nephrogenic diabetes insipidus (NDI) were recognized, and the concept was extended to resistance to other substances such as calcium ions in familial hypocalciuric hypercalcemia (FHH). Later, diseases characterized by excess rather than deficient hormone action such as McCune-Albright syndrome (MAS) and familial male precocious puberty (FMPP) were recognized to be caused by autonomous endocrine hyperfunction. Although many i!!vestigators provided careful and detailed descriptions of the clinical features of these and other related endocrine disorders, an understanding of pathogenesis proved elusive for many years. In just the past few years, we have gone from clinical description to a molecular understanding of these interesting disorders. This remarkable progress reflects a synthe­ sis of three distinct, but now overlapping, areas of biomedical research: the aforemen­ tioned recognition and careful clinical description of specific diseases, the elucidation of the basic mechanisms of signal transduction, and the application of the powerful tools of molecular biology and genetics. Fundamental studies on the mechanisms of hormone action by Rodbell and colleagues at NIH culminated in the discovery of a major signal transduction pathway involving heterotrimeric G proteins.

Zusammenfassung
This collection summarizes in-depth the state of knowledge concerning how cells communicate via G-protein-coupled signal transduction and how defects in these proteins and their receptors can cause serious human disease involving many different organ systems.