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Study · Animal study (in vivo) · rabbit · 2014

1 result

Validation of serum IGF-I as a biomarker to monitor the bioactivity of exogenous growth hormone agonists and antagonists in rabbits.

Bielohuby M, Zarkesh-Esfahani SH, Manolopoulou J, Wirthgen E, Walpurgis K, Toghiany Khorasgani M, Aghili ZS, Wilkinson IR, Hoeflich A, Thevis M, Ross RJ, Bidlingmaier M

Disease models & mechanisms19 Sept 2014Cited by 13 (Europe PMC)

PMID25239917 (opens in a new tab)PMCIDPMC4213730 (opens in a new tab)DOI10.1242/dmm.016519 (opens in a new tab)PepBankPUB-25239917
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Summary

The development of new growth hormone (GH) agonists and growth hormone antagonists (GHAs) requires animal models for pre-clinical testing. Ideally, the effects of treatment are monitored using the same pharmacodynamic marker that is later used in clinical practice. However, intact rodents are of limited value for this purpose because serum IGF-I, the most sensitive pharmacodynamic marker for the action of GH in humans, shows no response to treatment with recombinant human GH and there is little evidence for the effects of GHAs, except when administered at very high doses or when overexpressed. As an alternative, more suitable model, we explored pharmacodynamic markers of GH action in intact rabbits. We performed the first validation of an IGF-I assay for the analysis of rabbit serum and tested precision, sensitivity, linearity and recovery using an automated human IGF-I assay (IDS-iSYS). Furthermore, IGF-I was measured in rabbits of different strains, age groups and sexes, and we monitored IGF-I response to treatment with recombinant human GH or the GHA Pegvisomant. For a subset of samples, we used LC-MS/MS to measure IGF-I, and quantitative western ligand blot to analyze IGF-binding proteins (IGFBPs). Although recovery of recombinant rabbit IGF-I was only 50% in the human IGF-I assay, our results show that the sensitivity, precision (1.7-3.3% coefficient of variation) and linearity (90.4-105.6%) were excellent in rabbit samples. As expected, sex, age and genetic background were major determinants of IGF-I concentration in rabbits. IGF-I and IGFBP-2 levels increased after single and multiple injections of recombinant human GH (IGF-I: 286±22 versus 434±26 ng/ml; P<0.01) and were highly correlated (P<0.0001). Treatment with the GHA lowered IGF-I levels from the fourth injection onwards (P<0.01). In summary, we demonstrated that the IDS-iSYS IGF-I immunoassay can be used in rabbits. Similar to rodents, rabbits display variations in IGF-I depending on sex, age and genetic background. Unlike in rodents, the IGF-I response to treatment with recombinant human GH or a GHA closely mimics the pharmacodynamics seen in humans, suggesting that rabbits are a suitable new model to test human GH agonists and antagonists.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

1 result from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In rabbits, pegvisomant lowered IGF-I from the fourth injection onwards (P<0.01).

    In plain wordsIn rabbits, pegvisomant lowered IGF-I compared with before treatment from the fourth injection onwards.

    Peptide
    Pegvisomant
    Outcome
    DecreaseIGF-I after repeated injections
    Study

    rabbitn: not reported in source

    Intact rabbits
    Comparator
    Before treatment
    Outcome group
    Growth hormone and IGF-1 · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Treatment with the GHA lowered IGF-I levels from the fourth injection onwards (P<0.01).
    1 context sentence
    Summary · context
    Furthermore, IGF-I was measured in rabbits of different strains, age groups and sexes, and we monitored IGF-I response to treatment with recombinant human GH or the GHA Pegvisomant.

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Version history

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  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:34 UTC

    First added · source update from Europe PMC

Subjects

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