Absence of proteolysis of insulin-like growth factor binding protein-3 in serum from patients with growth hormone deficiency

Makoto Yamada, Tomonobu Hasegawa, Yukihiro Hasegawa

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Abstract

Insulin-like growth factor-I (IGF-I) is predominantly bound to IGF binding protein-3 (IGFBP-3), and free form of IGF-I (fIGF-I) may be bioactive in the circulation. Proteolysis of IGFBP-3, as reported in pregnant serum, results in the lowering of the affinity for IGF-I, thereby increasing the ratio of fIGF-I to total IGF-I (f/t IGF-I ratio). Conflicting results have been reported regarding the relationship between the proteolysis and growth hormone (GH)-IGF-I axis. Proteolysis of IGFBP-3 was previously reported to be present late at night in serum from pediatric subjects with GH receptor dysfunction (GHRD or 'Laron-type dwarfism'). Recently, it was reported that proteolysis of IGFBP-3 could not be detected in adult patients with GH deficiency (GHD). The purpose of this study was to investigate the possible relationship between proteolysis of IGFBP-3 and GH in patients with GHD including pediatric cases. Here, proteolysis of IGFBP-3 measured by Western immunoblotting (ages 4-25 years; n = 11) and f/t IGF-I ratio measured by immunoradiometric assay (ages 4-25 years; n= 10) were studied in patients with GHD, which is similar to GHRD in terms of lowered GH function. There was no significant proteolysis of IGFBP-3 in the sera from the 11 patients with GHD. No proteolysis of IGFBP-3 was observed during a 24 hour period in sera obtained every two hours from two patients with GHD. f/t IGF-I ratio was not increased in plasma from the 10 patients with GHD. Our data suggest that proteolysis of IGFBP-3 is independent of the GH-IGF-I axis.

Original languageEnglish
Pages (from-to)717-722
Number of pages6
JournalEndocrine journal
Volume46
Issue number5
DOIs
Publication statusPublished - 1999 Oct

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Keywords

  • Free/total IGF-I ratio
  • Growth hormone deficiency (GHD)
  • IGF binding protein-3 (IGFBP- 3)
  • Insulin-like growth factor-I (IGF-I)
  • Proteolysis of IGFBP-3
  • Western immunoblotting

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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