Absence of mutations in the growth hormone (GH)‐releasing hormone receptor gene in GH‐secreting pituitary adenomas

GH‐releasing hormone (GHRH) is a potent stimulator of somatotroph cell proliferation and GH secretion. GHRH acts via binding to a G‐protein coupled receptor (GPCR) (GHRH‐R), that activates adenylyl cyclase (AC) and increases growth and function of somatotroph cells. Indeed, a subset (30–40%) of somatotrophic adenomas contain somatic mutations of the GNAS1 gene that encodes the alpha subunit of the G‐protein (Gsα) that stimulates AC. As activating mutations of other GPCRs cause development of endocrine tumours, we hypothesized that somatic activating mutations of the GHRH‐R might provide the molecular basis for somatotroph cell proliferation in a subset of human GH‐secreting pituitary adenomas.