Comparison of Prostaglandin E1and TSH Stimulation of Cyclic AMP Synthesis in Thyroid Tissues from Euthyroid Subjects and Thyrotoxic Patients

Abstract

Possible differences of the mode of action of TSH and prostaglandin E1 (PGE) on the synthesis of cyclic AMP were studied in normal human thyroids (normal thyroid) and thyroids from thyrotoxic patients (toxic thyroid). TSH was less effective in toxic thyroids than in normal thyroids; whereas PGE1 was equally effective in normal thyroids and toxic thyroids. Since the basal level of cyclic AMP was the same in normal and toxic thyroids, this lower sensitivity of toxic thyroids to TSH was not due to the fact that toxic thyroids were already overactive in terms of cyclic AMP synthesis. The measurement of adenylate cyclase and phosphodiesterase activities in the plasma membranes or homogenates failed to explain this lower sensitivity of toxic thyroids to TSH. Small and large doses of T4 and T3 failed to suppress an increase of cyclic AMP produced by PGE1, in the slices and plasma membranes of normal and toxic thyroids; whereas large doses of T3 depressed an increase of cyclic AMP in response to TSH in the thyroid plasma membrane of toxic thyroids. When both TSH and PGE1 were administered simultaneously, an additive increase of cyclic AMP was found in normal thyroids and in toxic thyroids. From the data accumulated, we suggest that, although TSH and PGE1 stimulate cyclic AMP synthesis in normal and toxic thyroids, the site of action and/or mode of action of these two stimulators may possibly be different, at least in human thyroids.