QUANTIFICATION OF URINARY INSULIN-LIKE GROWTH-FACTORS (IGFS) AND IGF BINDING-PROTEIN-3 IN HEALTHY-VOLUNTEERS BEFORE AND AFTER STIMULATION WITH RECOMBINANT HUMAN GROWTH-HORMONE

We examined excretion of urinary insulin-like growth factors I and II (IGF-I and IGF-II) and their major binding protein IGFBP-3 in comparison to their respective serum concentration in nine healthy female volunteers (median age 25 years, range 22-27) under baseline conditions and after stimulation with recombinant human growth hormone (rhGH), 4.5 IU twice daily subcutaneously for a period of 3 days, The IGFs were measured in unconcentrated urine by use of recently developed, highly sensitive radioimmunoassays, The IGFBP-3 was measured by a specific radioimmunoassay, The mean (+/- SD) urinary concentrations of IGF-I (0.08 +/- 0.07 mu g/l), IGF-II (1.02 +/- 0.47 mu g/l) and IGFBP-3 (19.1. +/- 6.9 mu g/l) were two to three orders of magnitude lower than in serum. The ratio of IGF-II over IGF-I concentration in urine (13:1) was five times higher than in serum (2.5:1), and the ratio of IGFBP-3 over the sum of IGF-I and IGF-II in urine (17:1) was four times higher than in serum (4:1), Urinary excretion was 63.3 +/- 46.6 ng m(-2) 24 h(-1) for IGF-I, 1002 +/- 598 ng m(-2) 24 h(-1) for IGF-II and 18039 +/- 4983 ng m(-2) 24 h(-1) for IGFBP-3. Using fast protein liquid exclusion chromatography, only immunoreactive IGFBP-3 components of less than 60 kD were detected in urine, with a major peak at 20 kD, Urinary IGFBP-3 excretion correlated with serum IGFBP-3 (r = 0.61, p < 0.01) and the glomerular filtration rate (r = 0.56, p < 0.05) measured by steady-state inulin infusion clearances, Administration of rhGH stimulated significantly (p < 0.005) the serum IGF-I concentration by 50%, but not the urinary IGF-I excretion. In conclusion: the considerably higher ratio of IGF-II to IGF-T in urine compared to serum indicates that urinary IGF excretion does not represent only filtered IGFs, urinary IGF-I is a less sensitive indicator of GH activity than serum IGF-I, and as urinary IGFBP-3 excretion is in proportion to the glomerular filtration rate and serum IGFBP-3, it presumably reflects renal filtration of small immunoreactive IGFBP-3 fragments from the circulation.