THE MITOGENIC CASCADE OF CAMP IN THE THYR OID AND OTHER TISSUES

The study of cell proliferation control in the thyroid gland led us to define the mitogenic role of the cAMP cascade. TSH (thyroid stimulati ng hormone), via its binding to its receptor and activation of adenyla te cyclase increases the intracellular level of cAMP, leading to the s timulation of the function, the proliferation and the expression of di fferentiation in thyrocytes. The cAMP cascade is characterized by an e arly and transient rise of protooncogene c-MYC and JUNB expression. Th e tight kinetic regulation of these expressions could account for the apparently paradoxical coupling of mitogenesis and differentiation. Th e cyclic AMP mitogenic cascade is, down to the level of cyclins and th eir kinases, distinct from the growth factor activated cascades or the phorbol ester-protein kinase C cascade. In the cell types in which th e cAMP cascade stimulates function and proliferation, its constitutive activation would induce growth and hyperfunction, i.e. the generation of hyperfunctional autonomous adenoma or congenital hyperfunctions; i ts inactivation would lead to loss of function and atrophy of the orga n involved. Our present knowledge of the cAMP cascade and of its role thus allows us to predict the alterations of this pathway that could c ause hyperfunctional hyperplastic lesions or their converse counterpar t.