The GHRHR is a member of the class II B GPCR family, which couples predominantly to the Gs-adenylate cyclase-cAMP signaling pathway. Peptide hormones that activate class II GPCRs include GHRH, secretin, glucagon-like peptides, gastric-inhibitory peptide (GIP), pituitary adenylate cyclase-activating peptide, corticotropin-releasing hormone, vasoactive intestinal peptide, parathyroid hormone, and calcitonin-related peptides. GHRH, expressed in the arcuate nucleus of the hypothalamus and released into portal vasculature, directly stimulates growth hormone synthesis and secretion from the pituitary somatotropes by activating the corresponding GHRH receptors.