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Cloning of the growth hormone secretagogues receptor cDNA: new evidence for a third endocrine pathway controlling growth hormone release

The pulsatile secretion of growth hormone (GH) by the somatotrophs is controlled by at least two antagonistic hypothalamic peptides: somatostatin (SRIH) which inhibits GH release and growth hormone releasing hormone (GHRH) which stimulates GH release. Both peptides have been purified and well characterized. The mechanisms of action of these hypothalamic peptides has also been extensively studied and their receptors have been cloned. Both GHRH and SRIH receptors belong to the family of seven transmembrane receptors coupled to a heterotrimeric GTP-binding protein. The SRIH receptor is coupled to a Gi protein and its activation inhibits adenylate cyclase. On the other hand, the GHRH receptor is coupled to a Gs protein and its activation stimulates adenylate cyclase activity leading to increased cyclic AMP (cAMP) intracellular levels.

Recently, the discovery of new stimulators of GH secretion has led to the postulation of a third endocrine pathway controlling GH secretion. A synthetic hexapetide, termed