CLINICAL-SIGNIFICANCE AND MOLECULAR MECHANISMS OF BIOINACTIVE GROWTH-HORMONE (REVIEW)

About 80% of short children are not deficient in endogenous growth hor mone (GH) and termed idiopathic short stature (ISS). The causes of imp aired growth in children with ISS are various. Short stature and low i nsulin-like growth factor-I (IGF-I) concentration despite normal to hi gh GH concentration suggest impaired GH effect. The prototypical GH in sensitivity syndrome was described and characterized by the absent or defective GH receptors. Growth retardation resulting from biologically inactive GH was also described, but the molecular basis of biological ly inactive GH has remained unclear. Recently, two unique point mutati ons in the GH-1 gene in the children with short stature whose GH were supposed as bioinactive were reported. Mutant GH R77C not only failed to stimulate tyrosine phosphorylation by itself, but it also inhibited the activity of wild-type GH. This mutant GH exerted an antagonistic effect. Another mutant D112G was only bioinactive. This case was a typ ical Kowarski syndrome. The molecular heterogeneity of mutant GH refle cted clinical phenotype of bioinactive GH syndrome.