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Acute decrease in circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis

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Abstract

In thyrotoxicosis there is an impaired GH response to GHRH, normal GH responsiveness to GHRP-6 and lack of synergistic GH response after simultaneous administration of both peptides. We have previously shown that the GHRH-induced GH release in these patients increases after an acute reduction of circulating T3 values with administration of iopanoic acid, a compound that inhibits peripheral conversion of T4 to T3. We have now studied the effect of a decrease in serum T3 levels on the GH response to GHRP-6 (1 μg/kg) plus GHRH (100 μg) in 9 hyperthyroid patients before and after 15 days of treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (600 mg/day). Nine normal subjects were also studied. In all hyperthyroid patients iopanoic acid induced a rapid decrease and normalisation of serum T3 levels. In these subjects peak GH (μg/l; mean±SE) and AUC (μg/l·120 min) values after GHRP-6 plus GHRH were significantly higher on day 15 compared to pretreatment values (peak, 18.3±3.0 vs 13.4±1.9; AUC, 1227.9±212.9 vs 968.5±160.4; p&lt;0.05). Despite the significant enhancement of the GH responsiveness to GHRP-6 plus GHRH after treatment with iopanoic acid, this response remained significantly blunted when compared to controls both in terms of peak GH (18.3±3.0 vs 83.7±15.2; p<0.05) and AUC values (1227.9±212.9 vs 4956.5±889.3; p<0.05). In conclusion, our results show that an acute decrease of circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis. This could suggest that circulating T3 does not have a major role in the mechanisms involved in the synergistic effect of these peptides.

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References

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth hormone-releasing acylated peptide from stomach. Nature 1999, 402: 656–60.

    Article  PubMed  CAS  Google Scholar 

  2. Dieguez C, Foord SM, Peters JR, Hall R, Scanlon MF. The effects of thyroid hormone deprivation in vivo and in vitro on growth hormone (GH) responses to human pancreatic (tumor) GH-releasing factor (1–40) by dispersed rat anterior pituitary cells. Endocrinology 1985, 116: 1066–70.

    Article  PubMed  CAS  Google Scholar 

  3. Jones PM, Burrin JM, Ghatei MA, O’Halloran DJ, Legon S, Bloom SR. The influence of thyroid hormone status on the hypothalamo-hypophyseal growth hormone axis. Endocrinology 1990, 126: 1374–9.

    Article  PubMed  CAS  Google Scholar 

  4. Valcavi R, Zini M, Portioli I. Thyroid hormones and growth hormone secretion. J Endocrinol Invest 1992, 15: 313–30.

    PubMed  CAS  Google Scholar 

  5. Giustina A, Wehrenberg WB. Influence of thyroid hormones on the regulation of growth hormone secretion. Eur J Endocrinol 1995, 133: 646–53.

    Article  PubMed  CAS  Google Scholar 

  6. Yaffe BM, Samuels HH. Hormonal regulation of the growth hormone gene. J Biol Chem 1984, 259: 6284–91.

    PubMed  CAS  Google Scholar 

  7. Diamond DJ, Goodman HM. Regulation of growth hormone messenger RNA synthesis by dexametasone and triiodothyronine transcriptional rate and mRNA stability changes in pituitary tumor cells. J Mol Biol 1985, 181: 41–62.

    Article  PubMed  CAS  Google Scholar 

  8. Volpato CB, Nunes MT. Role of thyroid hormone in the control of growth hormone gene expression. Braz J Med Biol Res 1994, 27: 1269–72.

    PubMed  CAS  Google Scholar 

  9. Volpato CB, Nunes MT. Indirect evidence for a role of the 5’-monodeiodinase on the regulation of GH mRNA levels. Thyroid 1994, 4 (Suppl.): S–86.

    Google Scholar 

  10. Cattini PA, Anderson TR, Baxter JD, Mellon P, Eberhardt NL. The human growth hormone gene is negatively regulated by triiodothyronine when transfected into rat pituitary tumor cells. J Biol Chem 1986, 261: 13367–72.

    PubMed  CAS  Google Scholar 

  11. Chomczynski P, Soszynski PA, Frohman LA. Stimulatory effect of thyroid hormone on growth hormone gene expression in a human pituitary cell line. J Clin Endocrinol Metab 1993, 77: 281–5.

    PubMed  CAS  Google Scholar 

  12. Korytko AI, Cuttler L. Thyroid hormone and glucocorticoid regulation of pituitary growth hormone-releasing hormone receptor gene expression. J Endocrinol 1997, 152: R13–7.

    Article  PubMed  CAS  Google Scholar 

  13. Miki N, Ono M, Murata Y, et al. Thyroid hormone regulation of gene expression of the pituitary growth hormonereleasing factor receptor. Biochem Biophys Res Commun 1995, 217: 1087–93.

    Article  PubMed  CAS  Google Scholar 

  14. Tam SP, Lam KS, Srivastava G. Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism. Endocrinology 1996, 137: 418–24.

    PubMed  CAS  Google Scholar 

  15. Kamegai J, Tamura H, Ishii S, Sugihara H, Wakabayashi I. Thyroid hormones regulate pituitary growth hormone secretagogue receptor gene expression. J Neuroendocrinol 2001, 13: 275–8.

    Article  PubMed  CAS  Google Scholar 

  16. Petersenn S, Rasch AC, Penshorn M, Beil FU, Schulte HM. Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor. Endocrinology 2001, 142: 2649–59.

    PubMed  CAS  Google Scholar 

  17. Burgess JA, Smith BR, Merimee TJ. Growth hormone in thyrotoxicosis: effect of insulin-induced hypoglycemia. J Clin Endocrinol Metab 1966, 26: 1257–60.

    Article  PubMed  CAS  Google Scholar 

  18. Giustina A, Buffoli MG, Bussi AR, Wehrenberg WB. Acute effects of clonidine and growth-hormone-releasing hormone on growth hormone secretion in patients with hyperthyroidism. Horm Res 1991, 36: 192–5.

    Article  PubMed  CAS  Google Scholar 

  19. Giustina A, Schettino M, Bussi AR, et al. Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism. Horm Res 1992, 38: 256–9.

    Article  PubMed  CAS  Google Scholar 

  20. Valcavi R, Dieguez C, Zini M, Muruais C, Casanueva F, Portioli I. Influence of hyperthyroidism on growth hormone secretion. Clin Endocrinol 1993, 38: 515–22.

    Article  CAS  Google Scholar 

  21. Ramos-Dias JC, Yateman M, Camacho-Hübner C, Grossman A, Lengyel AMJ. Low circulating IGF-I levels in hyperthyroidism are associated with decreased GH response to GH-releasing hormone. Clin Endocrinol 1995, 43: 583–9.

    Article  CAS  Google Scholar 

  22. Giustina A, Ferrari C, Bodini C, et al. Effects of methimazole treatment on growth hormone (GH) response to GHreleasing hormone in patients with hyperthyroidism. Acta Endocrinol (Copenh) 1990, 123: 613–8.

    CAS  Google Scholar 

  23. Ramos-Dias JC, Lengyel AMJ. Iopanoic acid-induced decrease of circulating T3 causes a significant increase in GH responsiveness to GH releasing hormone in thyrotoxic patients. Clin Endocrinol (Oxf) 1999, 51: 461–7.

    Article  CAS  Google Scholar 

  24. Wu SY, Chopra IJ, Solomon DH, Johnson DE. The effect of repeated administration of ipodate (Oragrafin) in hyperthyroidism. J Clin Endocrinol Metab 1978, 47: 1358–62.

    Article  PubMed  CAS  Google Scholar 

  25. Bal C, Nair N. The therapeutic efficacy of oral cholecystographic agent (iopanoic acid) in the management of hyperthyroidism. J Nucl Med 1990, 31: 1180–2.

    PubMed  CAS  Google Scholar 

  26. Bürgi H, Wimpfheimer C, Burger A, Zaunbauer W, Rosler H, Lemarchand-Béraud T. Changes of circulating thyroxine, triiodothyronine, and reverse triiodothyronine after radiographic contrast agents. J Clin Endocrinol Metab 1976, 43: 1203–10.

    Article  PubMed  Google Scholar 

  27. Kaplan MM, Utiger RD. Iodothyronine metabolism in rat liver homogenates. J Clin Invest 1978, 61: 459–71.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. St Germain DL. Dual mechanisms of regulation of Type I iodothyronine 5’-deiodinase in the rat kidney, liver, and thyroid gland. Implications for the treatment of hyperthyroidism with radiographic contrast agents. J Clin Invest 1988, 81: 1476–84.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Larsen PR, Dick TE, Markovitz BP, Kaplan MM, Gard TG. Inhibition of intrapituitary thyroxine to 3,5,3’-triiodothyronine conversion prevents the acute suppression of thyrotropin release by thyroxine in hypothyroid rats. J Clin Invest 1979, 64: 117–28.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Kaplan MM. Thyroxine 5’-monodeiodination in rat anterior pituitary homogenates. Endocrinology 1980, 106: 567–76.

    Article  PubMed  CAS  Google Scholar 

  31. Ramos-Dias JC, Pimentel-Filho F, Reis AF, Lengyel AMJ. Different growth hormone (GH) responses to GH-releasing peptide and GH-releasing hormone in hyperthyroidism. J Clin Endocrinol Metab 1996, 81: 1343–6.

    PubMed  CAS  Google Scholar 

  32. Vieira JGH, Lombardi MT, Nishida SK. Monoclonal antibody- based immunoenzymometric assay for serum human growth hormone. Braz J Med Biol Res 1990, 23: 293–6.

    PubMed  CAS  Google Scholar 

  33. Sharp B, Reed AW, Tamagna EI, Geffner DL, Hershman JM. Treatment of hyperthyroidism with sodium ipodate (Orografin) in addition to propylthiouracil and propranolol. J Clin Endocrinol Metab 1981, 53: 622–5.

    Article  PubMed  CAS  Google Scholar 

  34. Escobar-Morreale HF, Obregón MJ, Hernández A, Escobar del Rey F, Morreale de Escobar G. Regulation of iodothyronine deiodinase activity as studied in thyroidectomized rats infused with thyroxine or triiodothyronine. Endocrinology 1997, 138: 2559–68.

    Article  PubMed  CAS  Google Scholar 

  35. Yeung RTT. Effect of propranolol on plasma growth hormone response in insulin-induced hypoglycemia in thyrotoxic patients. J Clin Endocrinol Metab 1973, 37: 968–71.

    Article  PubMed  CAS  Google Scholar 

  36. Valcavi R, Dieguez C, Zini M, et al. Effect of pyridostigmine and pirenzepine on GH responses to GHRH in hyperthyroid patients. Clin Endocrinol 1991, 35: 141–4.

    Article  CAS  Google Scholar 

  37. Cheng K, Chan WW, Barreto A Jr, Convey EM, Smith RG. The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys- NH2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3’,5’-monophosphate accumulation in rat primary pituitary cell culture. Endocrinology 1989, 124: 2791–8.

    Article  PubMed  CAS  Google Scholar 

  38. Bowers CY, Sartor AO, Reynolds GA, Badger TM. On the actions of the growth hormone-releasing hexapeptide, GHRP. Endocrinology 1991, 128: 2027–35.

    Article  PubMed  CAS  Google Scholar 

  39. Korbonits M, Grossman AB. Growth hormone-releasing peptide and its analogues. Novel stimuli to growth hormone release. Trends Endocrinol Metab 1995, 6: 43–9.

    Article  PubMed  CAS  Google Scholar 

  40. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996, 273: 974–7.

    Article  PubMed  CAS  Google Scholar 

  41. Smith RG, Pong S-S, Hickey GJ, et al. Modulation of pulsatile GH release through a novel receptor in hypothalamus and pituitary gland. Recent Prog Horm Res 1996, 51: 261–86.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Endocrinology, Universidade Federal de São Paulo, UNIFESP/EPM, Rua Pedro de Toledo, 910, 04039-002, São Paulo, SP, Brazil

    S. O. Nascif & Ana-M. J. Lengyel MD

  2. Division of Endocrinology, Faculdade de Ciências Médicas, Sorocaba/SP, São Paulo, Brazil

    M. H. Senger & J. C. Ramos-Dias

Authors
  1. S. O. Nascif
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  2. M. H. Senger
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  3. J. C. Ramos-Dias
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  4. Ana-M. J. Lengyel MD
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Correspondence to Ana-M. J. Lengyel MD.

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Nascif, S.O., Senger, M.H., Ramos-Dias, J.C. et al. Acute decrease in circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis. J Endocrinol Invest 26, 733–737 (2003). https://doi.org/10.1007/BF03347355

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