Inhibitory Action of Thyroid Hormone on the Activation of Adenyl Cyclase-Cyclic AMP System by Thyroid-Stimulating Hormone in Human Thyroid Tissues from Euthyroid Subjects and Thyrotoxic Patients

Abstract

The regulatory role of thyroid hormone on the adenyl cyclase-adenosine 3′,5′-monophosphate (cyclic AMP) system in human thyroid slices and plasma membranes from euthyroid subjects and thyrotoxic patients were studied by measuring the formation and accumulation of labeled and cold cyclic AMP. TSH stimulated adenyl cyclase-cyclic AMP system of the thyroid from euthyroid subjects and thyrotoxic patients, but the response was less in the thyroid from thyrotoxic patients. Small (10−9M) or large (10−4M) doses of thyroxin (T4) and triiodothyronine (T3) decreased the TSH-stimulated elevation of labeled and cold cyclic AMP level in the thyroid from euthyroid subjects. In contrast, graded doses of T4 (10−5 to 10−8M) and T3 (10−6 to 10−7M) failed to depress TSH-stimulated elevation of 3H cyclic AMP level in the thyroid from thyrotoxic patients. Large doses of T4 (10−4M) and T3 (10−4 and 10−5M) depressed TSH-stimulated adenyl cyclase activity, however. Since large doses of iodide and d-T4 have no effect on adenyl cyclase activity of the thyroid, and since T4 did not affect cyclic AMP accumulation of fat pads produced by catecholamine, it is suggested that thyroid hormones play an important role for the control of thyroid function through the depression of thyroidal adenyl cyclase-cyclic AMP system activated by TSH.