Mechanisms of action of somatostatin on human TSH-secreting adenoma cells

The mechanisms of somatostatin (SRIH) action on thyroid-stimulating hormone (TSH) secretion were examined using human TSH-secreting adenoma cells. SRIH (10(-7) M) inhibited TSH secretion through a pertussis toxin-sensitive G protein. SRIH also inhibited forskolin- and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP)-induced TSH secretion. The mechanisms of this inhibition were investigated by measuring intracellular Ca2+ concentration ([Ca2+]i) and by electrophysiological experiments. Application of 10(-7) M SRIH reduced the [Ca2+]i, whereas forskolin and 8-BrcAMP increased the [Ca2+]i. Simultaneous application of SRIH abolished the forskolin-and the 8-BrcAMP-induced [Ca2+]i increase, indicating that the SRIH-induced decrease in [Ca2+]i was independent of the reduction in intracellular cAMP. Under current clamp using the whole cell clamp, 10(-7) M SRIH hyperpolarized the membrane and arrested Ca(2+)-dependent action potentials, which accounted for the SRIH-induced decrease in [Ca2+]i. Voltage clamp...