Abstract
The insulin-like growth factors (IGF) arc potent polypeptide mitogens that are carried in the blood, primarily by a GH-dependent protein, IGF binding protein-3 (IGFBP-3). This IGFBP can be fragmented by IGFBP-proteases, subsequently altering the affinity for IGFs. We have characterised the serum and urine IGFBP profiles of children both pre- and post GH treatment. Techniques used were an IGFBP-3 RIA, Western ligand blot (WLB) and an IGFBP-3 protease assay. In the sera of pretreatment GHD children, IGFBP-3 levels were low by both RIA and WLB analysis, and there was no protease activity. Serum concentrations of IGFBP-3 were corrected following GH administration. In the urine, we have established a normal range of IGFBP-3 and IGFBP-3 protease activity in subjects between 5-44 years. Urinary IGFBP-3 (uIGFBP-3) is age-dependent, increasing from 40 ng/mg Cr to 60 ng/mg Cr at age 11-15, after which levels decline to 18 ng/mg Cr by 25 years. Furthermore, little uIGFBP-3 protease activity is delected. In pretreatment GHD subjects, immunoreactive uIGFBP-3 as determined by RIA were generally higher than age-matched controls, although there was some overlap with the normal range. Following GH therapy, uIGFBP-3 levels declined to within the normal range. This was in striking contrast to serum, where serum IGFBP-3 levels increased with GH administration. Although immunoreactive uIGFBP-3 were high, IGFBP-3 was undetectable by WLB. This difference was due to significant protease activity in these subjects, especially in the younger age groups. Following GH therapy, uIGFBP-3 became detectable by WLB and the protease activity diminished. Thus, in the urine of GHD children, an IGFBP-3 protease activity was delected that was apparently GH dependent. Furthermore, the urinary IGFBP-3 protease activity is a serine-type protease which is not metal ion dependent. The source of the IGFBP-3 protease is uncertain, although its appearance solely in the urine of GHD patients is a unique finding. Further assessment of this proteolytic activity may provide insight as to the renal function and clearance in GHD patients.
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Gargosky, S., Wilson, K., Anhalt, I. et al. IS IMMUNOREACTIVE IGFBP-3 IN THE URINE AN INDICATOR OF GROWTH HORMONE DEFICIENCY (GHD)?. Pediatr Res 33 (Suppl 5), S42 (1993). https://doi.org/10.1203/00006450-199305001-00236
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DOI: https://doi.org/10.1203/00006450-199305001-00236
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