AJP - Endocrinology and Metabolism, Vol 268, Issue 4 E558-E564, Copyright © 1995 by American Physiological Society

ARTICLES

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

K. Takano, M. Ajima, A. Teramoto, K. Hata and N. Yamashita
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.

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 experiments revealed that this membrane hyperpolarization resulted from the activation of an inward-rectifying K+ current through a pertussis toxin-sensitive G protein. Intracellular injection of cAMP (100 microM) through the patch pipette did not abolish the SRIH-induced K+ current, indicating that the activation of SRIH-induced K+ channels was independent of intracellular cAMP. From these data, we concluded that SRIH-induced membrane hyperpolarization was responsible for the [Ca2+]i decrease, which in turn inhibited TSH secretion. Application of thyrotropin-releasing hormone (TRH; 10(-7) M) caused an increase in the [Ca2+]i, composed of an initial transient increase followed by a sustained increase. SRIH inhibited the sustained increase in [Ca2+]i. SRIH also inhibited the TRH-induced decrease in the membrane conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

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