title: Absence of proteolysis of insulin-like growth factor binding protein-3 in serum from patients with growth hormone deficiency.
abstract: Insulin-like growth factor-I (IGF-I) is predominantly bound to IGF binding protein-3 (IGFBP-3), and free form of IGF-I (fIGF-I) may be bioactive in the circulation. Proteolysis of IGFBP-3, as reported in pregnant serum, results in the lowering of the affinity for IGF-I, thereby increasing the ratio of fIGF-I to total IGF-I (f/t IGF-I ratio). Conflicting results have been reported regarding the relationship between the proteolysis and growth hormone (GH)-IGF-I axis. Proteolysis of IGFBP-3 was previously reported to be present late at night in serum from pediatric subjects with GH receptor dysfunction (GHRD or "Laron-type dwarfism"). Recently, it was reported that proteolysis of IGFBP-3 could not be detected in adult patients with GH deficiency (GHD). The purpose of this study was to investigate the possible relationship between proteolysis of IGFBP-3 and GH in patients with GHD including pediatric cases. Here, proteolysis of IGFBP-3 measured by Western immunoblotting (ages 4-25 years; n=11) and f/t IGF-I ratio measured by immunoradiometric assay (ages 4-25 years; n=10) were studied in patients with GHD, which is similar to GHRD in terms of lowered GH function. There was no significant proteolysis of IGFBP-3 in the sera from the 11 patients with GHD. No proteolysis of IGFBP-3 was observed during a 24 hour period in sera obtained every two hours from two patients with GHD. f/t IGF-I ratio was not increased in plasma from the 10 patients with GHD. Our data suggest that proteolysis of IGFBP-3 is independent of the GH-IGF-I axis.
authors.affiliation: Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D010450:Endopeptidases / Q000097:blood*; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D015592:Immunoradiometric Assay; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011247:Pregnancy
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D010450:Endopeptidases