MEASUREMENT OF SERUM EXON 3-RETAINING GROWTH HORMONE-BINDING PROTEIN IN CHILDREN AND ADOLESCENTS BY RADIOIMMUNOASSAY

Recently described assays for the determination of growth hormone-bind ing protein (GHBP) show a wide variety of normal ranges. Their results depend on the assay design and in the case of ligand-immunofunctional assay (LIFA), probably also on the binding characteristics, i.e. epit ope specificity and affinity of the employed antibody. These facts und erline the necessity to look for more accurate and specific assays, In this report we describe an accurate and simple radioimmunoassay (RIA) which allows the specific quantitation of the exon 3-retaining GHBP i soform (E3-GHBP). Data of the E3-GHBP RIA were compared to those of a LIFA measuring undifferentiated functional forms of GHBP. Our results demonstrate significant relationships between GHBP and age, BMI and IG F-I as determined by RTA and by LIFA in normal children and adolescent s (n = 115, p < 0.001). Moreover, BMI is the only regulating factor of GHBP for both methods as shown by multiple regression analysis (p < 0 .001). All our data suggest a qualitatively paralleled regulation of E 3-GHBP and undifferentiated functional GHBP forms, This finding was co nfirmed by a good correlation between RIA and LIFA data (r = 0.74, p < 0.001). Children with idiopathic short stature (ISS, n = 47) had sign ificantly lower GHBP levels than normal controls (n = 58) measured by the E3-GHBP RIA (p < 0.0001) and by LIFA (p < 0.01), We conclude that (1) ISS children may have a structural or quantitative defect at the l evel of the GHR, and (2) the highly specific assay for E3-GHBP immunor eactivity provides a sensitive diagnostic tool in conditions with part ial GH insensitivity.