Deficiency of the Circulating Insulin-like Growth Factor System Associated with Inactivation of the Acid-Labile Subunit Gene.

DOMENÉ HM; BENGOLEA SV; MARTINEZ A; ROPELATO MG; PENNISI P; SCAGLIA P; HEINRICH JJ; JASPER HG

NEW ENGLAND JOURNAL OF MEDICINE

Massachusetts Medical Society.

Lugar: Boston, MS USA; Año: 2004 vol. Feb5 p. 570 - 577

0028-4793

The growth-promoting actions of growth hormone were originally hypothesized to be mediated through a circulating liver-generated sulfation factor that later came to be known as insulin-like growth factor I (IGF-I). This growth factor is produced in almost every tissue in the body. In the cartilage growth plate, growth hormone–induced IGF-I acts locally through autocrine–paracrine mechanisms. Some 80 to 85 percent of IGF-I circulates as a 150-kD ternary complex that includes the ligand itself, IGF-binding protein 3, and an acid-labile subunit. The acid-labile subunit is a glycoprotein found almost exclusively in the circulation and produced in the liver under growth hormone stimulation. This subunit stabilizes the IGF–IGF-binding protein 3 complex, reduces the passage of IGF-I to the extravascular compartment, and extends its half-life. Recently, the role of circulating IGF-I in growth has been challenged by the finding that specific disruption of the hepatic igf1 gene in mice, the main source of circulating IGF-I,or the inactivation of the gene encoding the acid-labile subunit protein (igfals) in mice has a minor effect on growth, despite causing a profound reduction in the serum IGF-I level. In this report, we describe a 17-year-old boy who had a delayed onset of puberty, slow pubertal progress, and yet minimal slowing of his linear growth in association with an inactivation of the IGFALS gene.