Inhibition of Thyroid Adenylate Cyclase by Thyroid Hormone: A Possible Locus for the “Short-Loop” Negative Feedback Phenomenon1

Abstract

The effect of thyroid hormone on bovine thyroid plasma membrane adenylate cyclase activity was studied in order to determine if the locus of the previously observed “short-loop” negative feedback in the thyroid (J Clin Invest 57: 745, 1976) is the adenylate cyclase enzyme system. Adenylate cyclase activity was measured in bovine thyroid plasma membrane. This preparation was responsive to TSH (100 mU/ml), PGE2 (5 × 10−M) and F− (10−2M) with increases in activity of 70%, 50%, and 1,000% over basal (1.3 ± 0.5 pmol cAMP formed/10 min/mg protein), respectively. L-Thyroxine (T4), 3,5,3′-triiodothyronine (T3), D-thyroxine, 3,5,3′-triiodothyroacetic acid, and 3,3′,5′-triiodothyronine inhibited basal adenylate cyclase activity by 25-35% in contrast, only T4, T3, and D-T4 inhibited TSH- and PGE2-stimulated adenylate cyclase activity. F− stimulation was unaffected. Lubrol-PX, non-ionic detergent, abolished TSH-induced adenylate cyclase activity, but plasma membrane so treated was still responsive to PGE2 and F−. Thy...