Understanding the pathogenesis of these adenomas will elucidate how biologic behavior affects acromegaly treatment outcomes.<h4>Evidence acquisition</h4>We searched PubMed for relevant English-language original research and review articles on signaling pathways and molecular drivers implicated in the pathogenesis of nonfamilial somatotroph adenomas in patients with acromegaly.<h4>Evidence synthesis</h4>Somatotroph cells express cognate G protein-coupled receptors for both hypothalamic stimulatory GH-releasing hormone (GHRH) and inhibitory somatostatin. This evidence concerns the gene GHRH and growth hormone secreting pituitary adenoma 1.