Skip to main content

Advertisement

SpringerLink
Log in

Supra-physiological rhGH administration induces gender-related differences in the hypothalamus–pituitary–thyroid (HPT) axis in healthy individuals

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

The use of recombinant human growth hormone (rhGH) is a common habit among athletes. While the effects of rhGH administration have been described with contrasting results in males, no data exist in females to date. The aim of the present study was to evaluate the effects of rhGH administration on TSH, FT4 and FT3 levels and the time requested to return to baseline values after treatment withdrawal.

Methods

Twenty-one healthy trained male and female athletes were treated with 0.03 mg rhGH/kg body mass 6 days/week for 3 weeks. We collected blood samples immediately before the first daily rhGH administration, at 3, 4, 8, 15 and 21 days of treatment and at 3 and 9 days after rhGH withdrawal.

Results

In males, rhGH administration induced a significant (p < 0.01) early and stable TSH decrease and IGF-I increase, and a delayed FT4 reduction without FT3 modification, suggesting a central regulatory mechanism. In females, rhGH administration induced a significant (p < 0.01) early and transient TSH decrease and IGF-I increase, and a transient reduction in FT4 without any changes in FT3 concentrations. rhGH withdrawal was associated with a prompt normalization of TSH and FT4 levels in males, while in females the effects of rhGH treatment had already disappeared during the last period of treatment.

Conclusion

We suggest that rhGH inhibits TSH at central level both in males and females. The pattern of normalization was different in the two genders probably due to gonadal steroids modulation on GH-IGF-I axis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. McHugh CM, Park RT, Sönksen PH, Holt RI (2005) Challenges in detecting the abuse of growth hormone in sport. Clin Chem 51:1587–1593

    Article  CAS  PubMed  Google Scholar 

  2. Di Luigi L, Rossi C, Sgrò P, Fierro V, Romanelli F, Baldari C, Guidetti L (2007) Do non-steroidal anti-inflammatory drugs influence the steroid hormone milieu in male athletes? Int J Sports Med 28:809–814

    Article  CAS  PubMed  Google Scholar 

  3. Di Luigi L (2008) Supplements and the endocrine system in athletes. Clin Sports Med 27:131–151

    Article  PubMed  Google Scholar 

  4. Di Luigi L, Baldari C, Pigozzi F, Emerenziani GP, Gallotta MC, Iellamo F, Ciminelli E, Sgrò P, Romanelli F, Lenzi A, Guidetti L (2008) The long-acting phosphodiesterase inhibitor tadalafil does not influence athletes’ VO2max, aerobic, and anaerobic thresholds in normoxia. Int J Sports Med 29:110–115

    Article  PubMed  Google Scholar 

  5. Di Luigi L, Sgrò P, Baldari C, Gallotta MC, Emerenziani GP, Crescioli C, Bianchini S, Romanelli F, Lenzi A, Guidetti L (2012) The phosphodiesterases type 5 inhibitor tadalafil reduces the activation of the hypothalamus–pituitary–adrenal axis in men during cycle ergometric exercise. Am J Physiol Endocrinol Metab 302:E972–E978

    Article  CAS  PubMed  Google Scholar 

  6. Holt RI, Sönksen PH (2008) Growth hormone, IGF-I and insulin and their abuse in sport. Br J Pharmacol 154:542–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sartorio A, Agosti F, Marazzi N, Maffiuletti NA, Cella SG, Rigamonti AE, Guidetti L, Di Luigi L, Muller EE (2004) Combined evaluation of resting IGF-I, N-terminal propeptide of type III procollagen (PIIINP) and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels might be useful for detecting inappropriate GH administration in athletes: a preliminary report. Clin Endocrinol (Oxf) 61:487–493

    Article  CAS  Google Scholar 

  8. Saugy M, Robinson N, Saudan C, Baume N, Avois L, Mangin P (2006) Human growth hormone doping in sport. Br J Sports Med 40:i35–i39

    Article  PubMed  PubMed Central  Google Scholar 

  9. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine Society (2011) Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1587–1609

    Article  CAS  PubMed  Google Scholar 

  10. Sato T, Suzukui Y, Taketani T, Ishiguro K, Masuyama T (1977) Enhanced peripheral conversion of thyroxine to triiodothyronine during hGH therapy in GH deficient children. J Clin Endocrinol Metab 45:324–329

    Article  CAS  PubMed  Google Scholar 

  11. Hussain MA, Schmitz O, Jorgensen JO, Christiansen JS, Weeke J, Schmid C, Froesch ER (1996) Insulin-like growth factor I alters peripheral thyroid hormone metabolism in humans: comparison with growth hormone. Eur J Endocrinol 134:563–567

    Article  CAS  PubMed  Google Scholar 

  12. Porretti S, Giavoli C, Ronchi C, Lombardi G, Zaccaria M, Valle D, Arosio M, Beck-Peccoz P (2002) Recombinant human GH replacement therapy and thyroid function in a large group of adult GH-deficient patients: when does L-T(4) therapy become mandatory? J Clin Endocrinol Metab 87:2042–2045

    Article  CAS  PubMed  Google Scholar 

  13. Oliner L, Ballantine JJ (1968) Effect of human growth hormone on thyroidal secretion, radiothyroxine turnover and transport in man. J Clin Endocrinol Metab 28:603–607

    Article  CAS  PubMed  Google Scholar 

  14. Grunfeld C, Sherman BM, Cavalieri RR (1988) The acute effects of human growth hormone administration on thyroid function in normal men. J Clin Endocrinol Metab 67:1111–1114

    Article  CAS  PubMed  Google Scholar 

  15. Møller J, Jørgensen JO, Møller N, Christiansen JS, Weeke J (1992) Effects of growth hormone administration on fuel oxidation and thyroid function in normal man. Metabolism 41:728–731

    Article  PubMed  Google Scholar 

  16. Giannoulis MG, Boroujerdi MA, Powrie J, Dall R, Napoli R, Ehrnborg C, Pentecost C, Cittadini A, Jørgensen JO, Sonksen PH, GH-2000 Study Group (2005) Gender differences in growth hormone response to exercise before and after rhGH administration and the effect of rhGH on the hormone profile of fit normal adults. Clin Endocrinol (Oxf) 62:315–322

    Article  CAS  Google Scholar 

  17. Leite NT, Salvatori R, Alcântara MR, Alcântara PR, Oliveira CR, Oliveira JL, Anjos-Andrade FD, Farias MI, Britto CT, Nóbrega LM, Nascimento AC Jr, Alves ÉO, Pereira RM, Campos VC, Menezes M, Martinelli CE Jr, Aguiar-Oliveira MH (2012) Effects of depot growth hormone replacement on thyroid function and volume in adults with congenital isolated growth hormone deficiency. J Endocrinol Invest 35:265–268

    CAS  PubMed  Google Scholar 

  18. Behan LA, Monson JP, Agha A (2011) The interaction between growth hormone and the thyroid axis in hypopituitary patients. Clin Endocrinol (Oxf) 74:281–288

    Article  CAS  Google Scholar 

  19. Lange KH, Isaksson F, Rasmussen MH, Juul A, Bülow J, Kjaer M (2001) GH administration and discontinuation in healthy elderly men: effects on body composition, GH-related serum markers, resting heart rate and resting oxygen uptake. Clin Endocrinol (Oxf). 55:77–86

    Article  CAS  PubMed  Google Scholar 

  20. Portes ES, Oliveira JH, MacCagnan P, Abucham J (2000) Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children. Clin Endocrinol (Oxf). 53:183–189

    Article  CAS  PubMed  Google Scholar 

  21. Glynn N, Agha A (2012) Diagnosing growth hormone deficiency in adults. Int J Endocrinol. 2012:972617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bermann M, Jaffe CA, Tsai W, DeMott-Friberg R, Barkan AL (1994) Negative feedback regulation of pulsatile growth hormone secretion by insulin-like growth factor I Involvement of hypothalamic somatostatin. J Clin Invest 94:138–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kanatsuka A, Makino H, Matsushima Y, Osegawa M, Yamamoto M, Kumagai A (1979) Effect of hypophysectomy and growth hormone administration on somatostatin content in the rat hypothalamus. Neuroendocrinology 29:186–190

    Article  CAS  PubMed  Google Scholar 

  24. Ghigo MC, Torsello A, Grilli R, Luoni M, Guidi M, Cella SG, Locatelli V, Müller EE (1997) Effects of GH and IGF-I administration on GHRH and somatostatin mRNA levels: I. A study on ad libitum fed and starved adult male rats. J Endocrinol Invest 20:144–150

    Article  CAS  PubMed  Google Scholar 

  25. Beck-Peccoz P, Lania A, Beckers A, Chatterjee K, Wemeau JL (2013) 2013 European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur Thyroid J. 2:76–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hackney AC, Kallman A, Hosick KP, Rubin DA, Battaglini CL (2012) Thyroid hormonal responses to intensive interval versus steady-state endurance exercise sessions. Hormones 11:54–60

    PubMed  Google Scholar 

  27. Rone JK, Dons RF, Reed HL (1992) The effect of endurance training on serum triiodothyronine kinetics in man: physical conditioning marked by enhanced thyroid hormone metabolism. Clin Endocrinol 37:325–330

    Article  CAS  Google Scholar 

  28. Agha A, Walker D, Perry L, Drake WM, Chew SL, Jenkins PJ, Grossman AB, Monson JP (2007) Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients. Clin Endocrinol (Oxf) 66:72–77

    CAS  Google Scholar 

  29. Ciloglu F, Peker I, Pehlivan A, Karacabey K, Ilhan N, Saygin O, Ozmerdivenli R (2005) Exercise intensity and its effects on thyroid hormones. Neuro Endocrinol Lett 26:830–834

    CAS  PubMed  Google Scholar 

  30. Curty FH, Lisbôa PC, Ortiga-Carvalho TM, Pazos-Moura CC (2000) The somatostatin analogue octreotide modulates Iodothyronine deiodinase activity and pituitary neuromedin B. Thyroid 10:647–652

    Article  CAS  PubMed  Google Scholar 

  31. Gereben B, Zeöld A, Dentice M, Salvatore D, Bianco AC (2008) Activation and inactivation of thyroid hormone by deiodinases: local action with general consequences. Cell Mol Life Sci 65:570–590

    Article  CAS  PubMed  Google Scholar 

  32. Jørgensen JO, Møller J, Laursen T, Orskov H, Christiansen JS, Weeke J (1994) Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotropin levels: studies in GH-deficient adults. Clin Endocrinol (Oxf) 41:609–614

    Article  Google Scholar 

  33. Sgrò P, Guidetti L, Crescioli C, Baldari C, Romanelli F, Bianchini S, D’Armiento M, Lenzi A, Di Luigi L (2010) Effect of supra-physiological dose administration of rhGH on pituitary–thyroid axis in healthy male athletes. Regul Pept 165:163–167

    Article  CAS  PubMed  Google Scholar 

  34. Atkinson H, England JA, Rafferty A, Jesudason V, Bedford K, Karsai L, Atkin SL (2013) Somatostatin receptor expression in thyroid disease. Int J Exp Pathol 94:226–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Djordjijevic D, Zhang J, Priam M, Viollet C, Gourdji D, Kordon C, Epelbaum J (1998) Effect of 17beta-estradiol on somatostatin receptor expression and inhibitory effects on growth hormone and prolactin release in rat pituitary cell cultures. Endocrinology 139:2272–2277

    CAS  PubMed  Google Scholar 

  36. Kimura N, Tomizawa S, Arai KN, Kimura N (1998) Chronic treatment with estrogen up-regulates expression of sst2 messenger ribonucleic acid (mRNA) but down-regulates expression of sst5 mRNA in rat pituitaries. Endocrinology 139:1573–1580

    CAS  PubMed  Google Scholar 

  37. Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA (1997) Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 82:550–555

    CAS  PubMed  Google Scholar 

  38. Münzer T, Rosen CJ, Harman SM, Pabst KM, St. Clair C, Sorkin JD, Blackman MR (2006) Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men. Am J Physiol Endocrinol Metab 290:E1006–E1013

    Article  CAS  PubMed  Google Scholar 

  39. Norman C, Rollene NL, Erickson D, Miles JM, Bowers CY, Veldhuis JD (2013) Estradiol regulates GH-releasing peptide’s interactions with GH-releasing hormone and somatostatin in postmenopausal women. Eur J Endocrinol 170:121–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Leung KC, Doyle N, Ballesteros M, Sjogren K, Watts CK, Low TH, Leong GM, Ross RJ, Ho KK (2003) Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proc Natl Acad Sci USA 100:1016–1021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit of Endocrinology, Department of Motor, Human and Health Sciences, University of Rome “Foro Italico”, Piazza Lauro de Bosis, 15, 00135, Rome, Italy

    P. Sgrò & L. Di Luigi

  2. Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    M. Sansone, A. Sansone, F. Romanelli & A. Lenzi

  3. Unit of Sports Medicine, Department of Motor, Human and Health Sciences, University of Rome “Foro Italico” , Piazza Lauro de Bosis, 15, 00135, Rome, Italy

    A. Parisi

  4. Experimental Laboratory for Auxo-endocrinological Research, Istituto Auxologico Italiano, Via Ariosto, 13, 20145, Milan, Italy

    A. Sartorio

Authors
  1. P. Sgrò
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Sansone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Parisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Sartorio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Sansone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Romanelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Lenzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. Di Luigi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Sgrò.

Ethics declarations

Conflict of interest

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.”

Informed consent

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sgrò, P., Sansone, M., Parisi, A. et al. Supra-physiological rhGH administration induces gender-related differences in the hypothalamus–pituitary–thyroid (HPT) axis in healthy individuals. J Endocrinol Invest 39, 1383–1390 (2016). https://doi.org/10.1007/s40618-016-0489-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-016-0489-6

Keywords

Search

Navigation