The mechanisms of paradoxical TRH response in human somatotroph adenoma cells were investigated using intracellular calcium measurement and static incubation assay. Intracellular calcium measurement revealed that TRH induces a biphasic response: a transient increase followed by a sustained plateau. The transient phase was due to the calcium release from IP(3)-regulated intracellular calcium store and the subsequent sustained phase was due to the calcium influx through the voltage-gated calcium channels. The signal transduction mechanism of the calcium plateau involved protein kinase C. These calcium responses, especially the second phase, was responsible for the TRH-induced GH release.
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