[Effect of various doses of biosynthetic growth hormone on levels of IGF-I binding protein 3 (IGFBP-3) in patients with hypopituitarism and growth hormone deficiency].

Abstract

Objectives: To study the effect of different doses of hGH (biosynthetic human growth hormone--Humatrope) administration on the profile of IGFBP-3 in hypopituitary patients with GHD and to find out the extent of production of IGFBP-3 proteases, which results in the elevated biological IGF-I activity.

Study design: Ten patients (after 1. collection) were randomized according to the dose of hGH, administered within three months, into group I: 3 micrograms/kg/day and group II: 6 micrograms/kg/day. After 2. collection the doses of hGH were in both groups duplicated and administered another three months (3. collection).

Methods: RIA's were used to analyse GH, IGF-I, total IGFBP-3 and fIGF-I. The profile of IGFBP-3 forms was studied by electrophoresis with western immunoblotting.

Results: Anabolic effect of administered hGH was demonstrated by significant increase of IGF-I and total IGFBP-3 in both groups of patients. It was evident that this increase is associated with the raise of proteolytic fragment of IGFBP-3 (29 kD).

Conclusion: The increased doses of hGH change the profile of IGFBP-3 in the sense of increasing concentrations of IGFBP-3 (29 kD). As proteolytic clipping of intact IGFBP-3 is associated with the raise of fIGF-I levels in individual patients it is possible to consider 29 kD IGFBP-3 as the marker of the therapy of hGH in our study. However, the increasing tendency to fIGF-I production after 2-fold higher administration of hGH in majority of patients in the trial is not in average significant so it means that the doses of hGH administered to each individual should be optimalized.