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Comparison of Prostaglandin E₁ and TSH Stimulation of Cyclic AMP Synthesis in Thyroid Tissues from Euthyroid Subjects and Thyrotoxic Patients

Department of Medicine, Institute of Adaptation Medicine Shinshu University, Matsumoto, Japan

Possible differences of the mode of action of TSH and prostaglandin E, (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 PGE, 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 PGE, 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 PGE, 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 PGE, 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.

Supported by a Grant from The Ministry oi Education of Japan.

Received July 22, 1974.