The growth hormone-insulin-like growth factor axis in kidney

Abstract

Growth hormone (GH) exerts a variety of metabolic and anabolic effects on skeletal and soft tissues including kidney. Some of these actions are mediated directly, whereas others result from GH-dependent synthesis and release of polypeptide growth factors designated insulin-like growth factors (IGFs). Receptors for GH are present in proximal tubule and GH directly stimulates gluconeogenesis at this site. IGF receptors are found in glomerulus and proximal tubule. Mechanisms for signal transduction by GH and IGFs have been characterized using proximal tubular basolateral membranes. IGFs regulate metabolic and transport processes in cultured glomerular mesangial cells and in isolated proximal tubular cells. IGF I is synthesized in cultured mesangial cells and is produced in a GH-dependent manner in cortical and medullary collecting duct. Evidence has accumulated that IGF I of renal origin functions as a paracrine growth factor in the settings of GH-induced hypertrophy and compensatory hypertrophy of the kidney, and in the setting of proximal tubular regeneration following ischemic injury. IGFs are embryonal mitogens and IGF II may act as a transforming agent for Wilms' tumor. Further characterization of the GH-IGF axis in kidney will provide additional insights into the roles of these peptides as regulators of renal function, growth, and development.