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Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women

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Abstract

Purpose

While a good safety for recombinant human growth hormone (rhGH) therapy at replacement doses is recognized, a possible link between high concentration of the GH-IGF-I axis hormones and side negative effect has been reported. The aim of this pilot study was to assess whether a short-term exposure to supra-physiological doses of rhGH may affect DNA integrity in human lymphocytes (PBL).

Methods

Eighteen healthy Caucasian female (24.2 ± 3.5 years) were randomly included in a Control (n = 9) and rhGH administration group (n = 9, 3-week treatment). DNA damage (comet assay), chromosomal breaks, and mitotic index in phytohemagglutinin-stimulated PBL were evaluated before (PRE), immediately (POST), and 30 days (POST30) after the last rhGH administration (0.029 mg kg− 1 BW; 6 days/week), together with serum IGF-1 and IGFBP-3 concentrations.

Results

rhGH administration increased IGF-I, without evidence of persisting IGF-I and IGFBP-3 changes 30 days after withdrawal. Total DNA breakage (% DNA in tails) was not significantly different in subjects treated with rhGH in comparison with controls, although the rhGH-treated subjects showed an higher percentage of heavily damaged nuclei immediately after the treatment (POST30 vs. PRE: p = 0.003), with a lower mitogenic potential of lymphocytes, detectable up to the POST30 (PRE vs. POST: p = 0.02; PRE vs. POST30: p = 0.007).

Conclusions

This pilot study showed that 3 weeks of short-term supra-physiological rhGH administration in healthy women induce a transient DNA damage and mitogenic impairment in PBL. The analysis of DNA damage should be explored as useful tool in monitoring the mid to long-term effects of high rhGH treatment or abuse.

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Acknowledgements

The authors acknowledge Dr. Serena Bianchini for the great support in laboratory’s activities and assays. This research was supported by grants of the Anti-Doping Commission (CVD) of the Italian Ministry of Health to Prof. Eugenio E. Muller (†Deceased) and to MP. The funders had not role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Unit of Biology, Department of Movement, Human and Health Sciences, Università di Roma “Foro Italico”, Piazza Lauro de Bosis, 15, 00135, Rome, Italy

    C. Fantini, M. Pittaluga, A. de Perini, I. Dimauro & D. Caporossi

  2. Unit of Endocrinology, Department of Movement, Human and Health Sciences, Università di Roma “Foro Italico”, 00135, Rome, Italy

    P. Sgrò & L. Di Luigi

  3. Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research, 20145, Milan, Italy

    A. Sartorio

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  1. C. Fantini
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Correspondence to D. Caporossi.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

Additional information

C. Fantini, P. Sgrò, D. Caporossi, and L. Di Luigi contributed equally to the study.

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Fantini, C., Sgrò, P., Pittaluga, M. et al. Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women. J Endocrinol Invest 40, 645–652 (2017). https://doi.org/10.1007/s40618-016-0603-9

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  • DOI: https://doi.org/10.1007/s40618-016-0603-9

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