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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 4 1206-1210
Copyright © 1998 by The Endocrine Society


Original Articles

No Effect of Growth Hormone on Serum Insulin-Like Growth Factor Binding Protein-3 Proteolysis1

Christian Skjærbæk, Andreas Kaal, Jens Møller, Nina Vahl, Jørgen Weeke, Hans Ørskov and Allan Flyvbjerg

Medical Research Laboratories (C.S., A.K., H.Ø., A.F.), Institute of Experimental Clinical Research, Aarhus University; and Medical Department M (J.M., N.V., J.W., A.F.), Aarhus Kommunehospital, DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Christian Skjærbæk, Medical Research Laboratories, Building 3, Aarhus Kommunehospital, 8000 Aarhus C, Denmark.

Abstract

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.




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