NO EFFECT OF GROWTH-HORMONE ON SERUM INSULIN-LIKE-GROWTH-FACTOR BINDING PROTEIN-3 PROTEOLYSIS

Increased proteolysis of insulin-like growth factor binding protein (I GFBP)-3 is seen in several pathophysiological conditions and may repre sent an important. mechanism for the regulation of insulin-like growth factor bioavailability. It has previously been suggested that proteol ysis of IGFBP-3 is dependent on the GH status. To investigate this, IG FBP-3 proteolysis was measured in three groups of subjects: 1) GH-defi cient patients before and after GH replacement (n = 14); 2) healthy su bjects before and after 14 days of GH administration (n = 7); and 3) a cromegalic patients before and after treatment with along-acting SRIH analogue (octreotide; n = 14). In vivo IGFBP-3 proteolysis was investi gated by Western immunoblotting. No difference was detected in pretrea tment samples, and GH treatment in GH-deficient subjects or octreotide treatment in acromegalic subjects had no impact on in vivo proteolysi s. In contrast. GH administration to healthy subjects caused a 21% inc rease in in vivo proteolysis (P = 0.0008). In vitro IGFBP-3 proteolysi s mas investigated by incubation of serum with I-125-rhIGFBP-3, follow ed by SDS-PAGE. In pretreatment samples, the percentage of proteolyzed I-125-rhIGFBP-3 was 13 +/- 1% (acromegalic subjects, 11 +/- 1% (healt hy subjects), and 9 +/- 1% (GH-deficient subjects) (P < 0.009, GH-defi cient os. acromegalic subjects). Treatment had no effect on in vitro p roteolysis. We conclude that GH status has no major impact on IGFBP-3 protease activity in serum.