Only five years ago, the cyclic 3 ‘, 5 ‘-AMP model of hormonal action was not generally believed to apply to TSH t and thyroid.’-* Since then, overwhelming evidence has been accumulating in favor of this hyp~ thesis.~ The cAMP concept, as it may apply to the thyroid is summarized in FIGURE 1. Four criteria have been proposed by Sutherland and his colleagues to test the validity of this model for a particular hormonal action:(1) the hormone should activate adenyl cyclase in homogenates of the target tissue or/and in sedimentable fractions of such homogenates;(2) the hormone should increase the cAMP content of intact target cells;(3) liposoluble derivatives of CAMP, such as DBcAMP, or even cAMP itself, should mimic the hormonal action on the target tissue; and (4) inhibitors of cAMP intracellular catabolism, ie, of cAMP phosphodiesterase (s), such as the methylxanthines, should reproduce or potentiate the hormonal effects.

For each hormonal effect, the kinetics and the concentration-response relationships should be consistent with the model. In this article we propose to summarize briefly the evidence supporting the validity of the cAMP model for TSH and thyroid, then to present data, mostly from our laboratory, on the mechanism of TSH-induced thyroid secretion.