The secretion of GH from pituitary somatotrophs is mainly regulated by alterations in the levels of intracellular free Ca(2+) concentrations ([Ca(2+)](i)) that depend on the influx of Ca(2+) through voltage-gated Ca(2+) channels in the cell membrane. Hypothalamic stimulatory and inhibitory factors bind to specific receptors on the cell membrane to regulate membrane potential and activate second-messenger systems. The receptors are G-protein coupled, and activated G proteins directly influence membrane ion channels to regulate Ca(2+) influx. The function of cAMP-dependent protein kinase A is also modulated by receptor-coupled G proteins leading to the phosphorylation of Ca(2+) channel proteins and further alteration of Ca(2+) influx.