No effect of growth hormone on serum insulin-like growth factor binding protein-3 proteolysis.
Increased proteolysis of insulin-like growth factor binding protein (IGFBP)-3 is seen in several pathophysiological conditions and may represent an important mechanism for the regulation of insulin-like growth factor bioavailability. It has previously been suggested that proteolysis of IGFBP-3 is dependent on the GH status. To investigate this, IGFBP-3 proteolysis was measured in three groups of subjects: 1) GH-deficient patients before and after GH replacement (n = 14); 2) healthy subjects before and after 14 days of GH administration (n = 7); and 3) acromegalic patients before and after treatment with a long-acting SRIH analogue (octreotide; n = 14). In vivo IGFBP-3 proteolysis was investigated by Western immunoblotting. No difference was detected in pretreatment samples, and GH treatment in GH-deficient subjects or octreotide treatment in acromegalic subjects had no impact on in vivo proteolysis. In contrast, GH administration to healthy subjects caused a 21% increase in in vivo proteolysis (P = 0.0008). In vitro IGFBP-3 proteolysis was investigated by incubation of serum with 125I-rhIGFBP-3, followed by SDS-PAGE. In pretreatment samples, the percentage of proteolyzed 125I-rhIGFBP-3 was 13 +/- 1% (acromegalic subjects), 11 +/- 1% (healthy subjects), and 9 +/- 1% (GH-deficient subjects) (P < 0.009, GH-deficient vs. acromegalic subjects). Treatment had no effect on in vitro proteolysis. We conclude that GH status has no major impact on IGFBP-3 protease activity in serum.
Skjaerbaek
C
C
Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University, Denmark.
Kaal
A
A
Møller
J
J
Vahl
N
N
Weeke
J
J
Orskov
H
H
Flyvbjerg
A
A
D000172:Acromegaly / Q000097:blood; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D008297:Male; D008875:Middle Aged
D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone