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
B. Tonshoff et al., 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, European journal of endocrinology, 132(4), 1995, pp. 433-437
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 comparis
on to their respective serum concentration in nine healthy female volu
nteers (median age 25 years, range 22-27) under baseline conditions an
d after stimulation with recombinant human growth hormone (rhGH), 4.5
IU twice daily subcutaneously for a period of 3 days, The IGFs were me
asured in unconcentrated urine by use of recently developed, highly se
nsitive radioimmunoassays, The IGFBP-3 was measured by a specific radi
oimmunoassay, 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 fiv
e times higher than in serum (2.5:1), and the ratio of IGFBP-3 over th
e sum of IGF-I and IGF-II in urine (17:1) was four times higher than i
n serum (4:1), Urinary excretion was 63.3 +/- 46.6 ng m(-2) 24 h(-1) f
or 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 ch
romatography, only immunoreactive IGFBP-3 components of less than 60 k
D 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 g
lomerular filtration rate (r = 0.56, p < 0.05) measured by steady-stat
e inulin infusion clearances, Administration of rhGH stimulated signif
icantly (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 I
GF excretion does not represent only filtered IGFs, urinary IGF-I is a
less sensitive indicator of GH activity than serum IGF-I, and as urin
ary IGFBP-3 excretion is in proportion to the glomerular filtration ra
te and serum IGFBP-3, it presumably reflects renal filtration of small
immunoreactive IGFBP-3 fragments from the circulation.