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Although the factors controlling the secretion of the neuropeptide somatostatin have been extensively studied, little is known about the mechanisms that control somatostatin biosynthesis. Somatostatin secretion is regulated by numerous agents that increase intracellular levels of cAMP. We sought to determine whether cAMP also regulates somatostatin mRNA accumulation. We found that forskolin elicited an increase in somatostatin secretion and mRNA levels in primary cultures of rat diencephalic cells. Another secretagogue, KCl, was as effective as forskolin in causing somatostatin secretion but had no effect on mRNA accumulation. Somatostatin expression in fibroblast cells transfected with the somatostatin gene was also regulated by forskolin. These results demonstrate that somatostatin mRNA accumulation can be regulated through a cAMP-dependent pathway, that this pathway is operative in heterologous cells transfected with the somatostatin gene, and that stimulation of somatostatin secretion and mRNA accumulation can be uncoupled from one another.

Cyclic AMP regulates somatostatin mRNA accumulation in primary diencephalic cultures and in transfected fibroblast cells