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.