Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors.

I. Cell Proliferation in Normal Thyroid Tissue In Vivo ............................................... A. Physiological situation ........................................................................... B. Growth under stimulatory conditions ........................................................... C. Coordination between various thyroid cell types ................................................ D. Stem cells ........................................................................................ II. Methodology and Model Systems for Study of Thyroid Growth ................................... A. Model systems ................................................................................... B. Methodology: indexes of cell proliferation ...................................................... C. Working definition: growth control ratio ........................................................ III. Differentiation, Determination, Differentiation Expression ....................................... A. Thyroid system .................................................................................. B. Model for thyroid ................................................................................ IV. Extracellular Signals Involved in Control of Proliferation of Thyroid Cells ....................... A. Thyrotropin ...................................................................................... B. Iodine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C. Other hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . D. Pathological signals .............................................................................. E. Local signals ..................................................................................... V. Pathways Regulating Thyroid Cell Proliferation ................................................... A. General considerations .......................................................................... B. Mitogenic and differentiating action of thyrotropin ............................................ C. Effect of factors other than thyrotropin on proliferation and differentiation ................. D. Role of adenosine 3’,5’-cyclic monophosphate, phosphatidylinositol bisphosphate, and tyrosine protein kinase cascades in thyrocyte proliferation ......................................... E. Kinetics of biochemical events in various thyroid mitogenic pathways ........................ F. Role of autocrine loop ............................................................................ VI. Apparently Opposite Programs: Proliferation and Differentiation Expression Are Induced by Thyrotropin and Adenosine 3’,5’-Cyclic Monophosphate Cascade .............................. VII. Growth Control and Goitrogenesis .................................................................. A. General concepts ................................................................................. B. Graves’ disease ................................................................................... C. Congenital defects ............................................................................... D. Thyroid adenoma ................................................................................ E. Sporadic goiter ................................................................................... VIII. Hypothetical and Existing Examples of Constitutive Activation of Adenosine 3’,5’-Cyclic Monophosphate Cascade ........................................................................ A. Adenylate cyclase-coupled receptors ............................................................ B. Cyclase-activating guanosine triphosphate-binding protein .................................... C. Adenosine 3’,5’-cyclic monophosphate-dependent protein kinase ............................... D. Negative controls of adenosine 3’,5’-cyclic monophosphate cascade ............................. IX. Conclusions .......................................................................................... 667 667 668 668 669 669 669 670 671 671 671 672 673 673 674 674 674 674 675 675 676 677