Assays for insulin-like growth factors and their binding proteins: Practicalities and pitfalls,☆☆,,★★

https://doi.org/10.1016/S0022-3476(96)70012-4Get rights and content

Abstract

Insulin-like growth factors (IGFs) are growth hormone-dependent anabolic peptides that circulate in biologic fluids complexed to a family of IGF binding proteins. Measurement of the serum concentrations of IGF peptides and IGF binding proteins has proved to be an effective means of evaluating functional growth hormone status and makes it possible to establish a diagnosis of IGF deficiency. (J PEDIATR 1996;128:S52-7)

Section snippets

MEASUREMENT OF IGFS

Assays for IGF peptides have evolved during the past 30 years from bioassays to competitive bioassays to various radioimmunoassays or their variants.1 Early bioassays depended on the ability of IGF peptides to stimulate proteoglycan synthesis, glucose or amino acid incorporation, or DNA synthesis. In addition to being time-consuming, these assays had a lack of specificity, because the biologic actions tested were stimulated by both IGF-I and IGF-II. Radioimmunoassays and their variants, such as

MEASUREMENT OF IGFBPS

It is now apparent that at least six different IGFBPs exist in serum. Virtually all cultured cells have been found to produce one or more IGFBPs, and IGFBPs have been identified in virtually all biologic fluids, including amniotic fluid, cerebrospinal fluid, urine, seminal fluid, and ovarian follicular fluid. The multiplicity of IGFBPs and the diversity of mechanisms involved in their regulation point to the concept that they have evolved to modulate the actions of IGF peptides in a variety of

CONCLUSIONS

The use of validated, rigorous assays for IGF-I, IGF-II, and the various IGFBPs provides a way of assessing the IGF axis and, indirectly, measuring functional GH secretion. As assays with greater specificity and sensitivity have been developed for the various components of the IGF system, and as proper attention has been paid to the necessity for rigorous performance of such assays, it has become apparent that measurements of the IGF axis have several important advantages over assays of GH

References (23)

  • Y Oh et al.

    Insulin-like growth factor (IGF)-independent action of IGF binding protein-3 in Hs578T human breast cancer cells

    J Biol Chem

    (1993)
  • RG Rosenfeld et al.

    Insulin-like growth factors I and II in evaluation of growth retardation

    J Pediatr

    (1986)
  • WH Daughaday et al.

    Insulin-like growth factors I and II: peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations

    Endocr Rev

    (1989)
  • J Guevara-Aguirre et al.

    A randomized, double-blind, placebo-controlled trial on safety and efficacy of recombinant human insulin-like growth factor-I in children with growth hormone receptor deficiency

    J Clin Endocrinol Metab

    (1995)
  • JI Jones et al.

    Insulin-like growth factors and their binding proteins: biological actions

    Endocr Rev

    (1995)
  • WF Blum et al.

    A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency

    J Clin Endocrinol Metab

    (1990)
  • RC Baxter

    Characterization of the acid-labile subunit of the growth hormone-dependent insulin-like growth factor binding protein complex

    J Clin Endocrinol Metab

    (1988)
  • P Hossenlopp et al.

    Evidence of enzymatic degradation of insulin-like growth factor binding proteins in the 150K complex during pregnancy

    J Clin Endocrinol Metab

    (1990)
  • LC Giudice et al.

    Insulin-like growth factor binding proteins in maternal serum throughout pregnancy and in the puerperium: effects of a pregnancy-associated serum protease activity

    J Clin Endocrinol Metab

    (1990)
  • JMP Holly et al.

    Proteases acting on IGFBPs: their occurrence and physiological significance

    Growth Regul

    (1993)
  • SE Gargosky et al.

    Measurement and characterization of insulin-like growth factor binding protein–3 in human biological fluids: discrepancies between radioimmunoassay and ligand blotting

    Endocrinology

    (1992)
  • Cited by (30)

    • Validation of a multiplexed LC–MS/MS clinical assay to quantify insulin-like growth factor-binding proteins in human serum and its application in a clinical study

      2019, Toxicology and Applied Pharmacology
      Citation Excerpt :

      Multiplexed immunoassays are associated with many challenges including the elimination of assay cross-reactivity, configuration of multi-analyte sensitivities, and achievement of working ranges that are biologically relevant for diverse matrices/physiological states (Gan and Patel, 2013; Hidi, 2010; Kingsmore, 2006). Variable antibody recognition of isoforms of IGFBP 1 and 3 (e.g., fragments, and altered phosphorylation and/or glycosylation) may result in false estimates of actual concentrations and/or inappropriate interpretations (Khosravi et al., 1997; Ocrant et al., 1992; Rosenfeld and Gargosky, 1996). Additionally, ELISA analysis of IGFBPs has been reported to be impaired by IGF binding (Boernsen et al., 2009).

    • Normal and Aberrant Growth in Children

      2015, Williams Textbook of Endocrinology
    • Normal and Aberrant Growth

      2011, Williams Textbook of Endocrinology, Twelfth Edition
    View all citing articles on Scopus

    From the Department of Pediatrics, Oregon Health Sciences University, Portland

    ☆☆

    Supported in part by Diagnostic Systems Laboratories, Inc., and by grant HD28703 from the National Institutes of Health.

    Reprint requests: Ron G. Rosenfeld, MD, Department of Pediatrics, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97062.

    ★★

    0022-3476/96/$5.00 + 0 9/0/72339

    View full text