Stimulating effect of forskolin on thyroxine secretion. Influence of calcium

The aim of this study was to determine, with a rat thyroid fragment perifusion system, the short-term (20 min) effect of forskolin (FK), an adenylate cyclase activator, on T4 secretion, the effect of forskolin on T4 secretion stimulated by theophylline and TSH, and the role played by calcium in the forskolin effect. A dose-dependent effect on T4 secretion was obtained with forskolin, from 10(-8) to 10(-4) mol/l, with a maximal effect between 10(-6) and 10(-5) mol/l. The effect of forskolin was not increased by theophylline. The combined stimulation with forskolin and theophylline induced a T4 release which remained significantly lower than the effect of 22 or 65 mIU/ml TSH. Forskolin slightly increased the stimulating effect of 22 mIU/ml TSH but significantly decreased the effect of 65 mIU/ml TSH. A reduction in the buffer calcium concentration slightly decreased the effect of the forskolin and theophylline stimulations and the effect of the combined stimulation with forskolin and theophylline without suppressing completely the effect of these stimulations. This study demonstrates that 1) low concentrations of forskolin are able to induce a significant T4 release during short-term stimulations; 2) calcium is necessary in order to obtain a maximum effect of adenylate cyclase activation on T4 release; 3) the part of the thyroid hormone response to TSH which is mediated by adenylate cyclase activation is relatively small.