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Lack of effect of hexarelin on TRH-induced TSH response in normal adult man

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Abstract

The mechanism of action of the synthetic growth hormone (GH)releasing peptide hexarelin is not yet fully understood. Although a direct effect on pituitary cells has been demonstrated, the peptide is also active at hypothalamic level, where specific binding sites have been found. The observation that hexarelin acts synergistically with GH-releasing hormone (GHRH) in releasing GH has suggested that it might suppress endogenous somatostatin secretion. As somatostatin is also inhibitory on TSH secretion, to verify the occurrence of modifications of the somatostatinergic tone induced by hexarelin, we studied its effects on TRH-induced TSH secretion. Seven normal subjects (4 women and 3 men aged 24–29 years) underwent the following tests on 3 different days: a) TRH (200 µg/l iv)+placebo; b) hexarelin (1 µg/Kg bw iv) +placebo c) combined TRH+hexarelin administration. Hexarelin induced significant and similar increases in serum GH levels when given in combination either with placebo or with TRH (1217±470 vs 986±208 µg/min/l p: NS), while no modifications of GH levels were seen after TRH+placebo. Serum TSH levels were unmodified by hexarelin+placebo injection. The TSH increase elicited by hexarelin+ TRH was superimposable to that elicited by TRH +placebo (1124±530 and 1273±380 mU/min/l respectively). Circulating PRL levels slightly increased after hexarelin+placebo too (897 µg/min/l), and the PRL response to hexarelin+TRH was slightly, although not significantly, greater than that observed after TRH+placebo (2680±1517 and 2243±1108 µg/min/l, respectively). In conclusion, our data show that hexarelin does not alter basal and TRH-stimulated TSH secretion, thus suggesting that it does not inhibit somatostatin release. Furthermore a modest PRL-releasing effect of this peptide has been confirmed.

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References

  1. Bowers C.Y. GH releasing peptides — structure and kinetics. J. Pediat. Endocrinol. 6: 21, 1993.

    Article  CAS  Google Scholar 

  2. Korbonits M., Grossman A.B. Growth hormone-releasing peptide and its analogues. Trends Endocrinol. Metab. 6: 43, 1995.

    Article  PubMed  CAS  Google Scholar 

  3. Ghigo E., Arvat E., Muccioli G., Camanni F. Growth hormone-releasing peptides. Eur. J. Endocrinol. 136: 445, 1997.

    Article  PubMed  CAS  Google Scholar 

  4. Howard A.D., Feighner S.D., Cully D.F., Arena J.P., Liberator P.A., Rosenblum L., Hamelin M., Hreniuk D.L., Palyha O.C., Anderson J., Paress P.S., Diaz C., Chou M., Liu K.K., McKee K.K., Pong S-S., Chaung L-Y., Elbrecht A., Dashkevicz M., Heaens R., Rigby M., Sirinathsinghji D.J.S., Dean D.C., Melillo D.G., Patchett A.A., Nargund A.A., Griffin P.R., DeMartino J.A., Gupt S.K., Schaeffer J.M., Smith R.G., Van der Ploeg L.H.T. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273: 974, 1996.

    Article  PubMed  CAS  Google Scholar 

  5. Conley L.K., Giustina A., Imbimbo B.P., Stagg L.C., Deghenghi R., Wehrenberg W.B. Hexarelin (His-D-2methyl-Trp-Ala-Trp-D- Phe- Lys-NH2), a new GH-releasing peptide, is biologically active in male and female rats. Endocrine J. (UK) 2: 691, 1994.

    CAS  Google Scholar 

  6. Deghenghi R., Cananzi M., Torsello A., Battisti C., Müller E.E., Locatelli V. GH-releasing activity of hexarelin, a new growth hormone releasing peptide, in infant and adults rats. Life Sci. 54: 1321, 1994.

    Article  PubMed  CAS  Google Scholar 

  7. Badger T.M., Millard W.J., McCormick G.F., Bowers C.Y., Martin J.B. The effects of growth hormone (GH)-releasing peptide on GH secretion in perifused pituitary cells of adult male rats. Endocrinology 115: 1432, 1984.

    Article  PubMed  CAS  Google Scholar 

  8. Bowers C.Y., Sartor A.O., Reynolds G.A., Badger T.M. On the actions of the growth hormone-releasing hexapeptide, GHRP. Endocrinology 128: 2027, 1991.

    Article  PubMed  CAS  Google Scholar 

  9. Hayashi S., Kaji H., Ohashi S., Abe H., Chihara K. Effect of intravenous administration of growth hormone-releasing peptide on plasma growth hormone in patients with short stature. Clin. Pediatr. Endocrinol. 2(Suppl 2): 69, 1993.

    Article  Google Scholar 

  10. Popovic V., Damjanovic S., Micic D., Djurovic M., Dieguez C., Casanueva F. Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level. J. Clin. Endocrinol. Metab. 80: 942, 1995.

    PubMed  CAS  Google Scholar 

  11. Bowers C.Y., Reynolds G.A., Durham D., Barrera C.M., Pezzoli S.S., Thorner M.O. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. J. Clin. Endocrinol. Metab. 70: 975, 1990.

    Article  PubMed  CAS  Google Scholar 

  12. Peñalva A., Carballo A., Pombo M., Casanueva F.F., Dieguez C. Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man. J. Clin. Endocrinol. Metab. 76: 168, 1993.

    PubMed  Google Scholar 

  13. DeBell W.K., Pezzoli S.S., Thorner M.O. Growth Hormone (GH) secretion during continuous infusion of GH-releasing peptide: partial response attenuation. J. Clin. Endocrinol. Metab. 72: 1312, 1991.

    Article  PubMed  CAS  Google Scholar 

  14. Giustina A., Bussi A.R., Deghenghi R., Imbimbo B., Licini M., Poiesi C., Wehrenberg W.B. Comparison of the effects of growth hormone-releasing hormone and hexarelin, a novel growth hormone-releasing peptide-6 analog, on growth hormone secretion in humans with or without glucocorticoid excess. J. Endocrinol. 146: 227, 1995.

    Article  PubMed  CAS  Google Scholar 

  15. Maccario M., Arvat E., Procopio M., Gianotti L., Grottoli S., Imbimbo B.P., Lenaerts V., Deghenghi R., Camanni F., Ghigo E. Metabolic modulation of the growth hormone-releasing activity of hexarelin in man. Metabolism 44: 134, 1995.

    Article  PubMed  CAS  Google Scholar 

  16. Clark R.G., Carlsson L.M.S., Trojnar J., Robinson I.C.A.F. The effects of a growth hormone-releasing peptide and growth hormone-releasing factor in conscious and anaesthetized rats. J. Neuroendocrinol. 1: 249, 1989.

    Article  PubMed  CAS  Google Scholar 

  17. Conley L.K., Teik J.A., Deghenghi R., Imbimbo B.P., Giustina A., Locatelli V., Wehrenberg W.B. Mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH and somatostatin in the rat. Neuroendocrinology 61: 44, 1995.

    Article  PubMed  CAS  Google Scholar 

  18. Alba-Roth J., Müller O.A., Schopohl J., vonWerder K. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J. Clin. Endocrinol. Metab. 67: 1186, 1988.

    Article  PubMed  CAS  Google Scholar 

  19. Jaffe C.A., Ho P.J., Demott-Friberg R., Bowers C.Y., Barkan A.L. Effects of a prolonged growth hormone (GH)-releasing peptide infusion on pulsatile GH secretion in normal men. J. Clin. Endocrinol. Metab. 77: 1641, 1993.

    PubMed  CAS  Google Scholar 

  20. Williams T.C., Kelijman M., Crelin W.C., Downs T.R., Frohman L.A. Differential effects of somatostatin (SRIH) and a SRIH analog, SMS 201–995, on the secretion of growth hormone and thyroid-stimulating hormone in man. J. Clin. Endocrinol. Metab. 66: 39, 1988.

    Article  PubMed  CAS  Google Scholar 

  21. Kelijman M., Frohman L.A. β-Adrenergic modulation of growth hormone (GH) autofeedback on sleep associates and pharmacologically induced GH secretion. J. Clin. Endocrinol. Metab. 69: 1187, 1989.

    Article  PubMed  CAS  Google Scholar 

  22. Freeman E., Touzel R., Grossman A., Besser M., Ross R. Pyridostigmine, an acetylcholinoesterase inhibitor, stimulates growth hormone release, but has no effect on basal thyrotrophin or adrenocorticotrophin levels, or the thyrotrophin response to thyrotrophin-releasing hormone. J. Neuroendocrinol. 2: 429, 1990.

    Article  PubMed  CAS  Google Scholar 

  23. Kelijman M., Frohman L.A. The role of the cholinergic pathway in growth hormone feedback. J. Clin. Endocrinol. Metab. 72: 1081, 1991.

    Article  PubMed  CAS  Google Scholar 

  24. Müller E.E. Cholinergic function and neural control of GH secretion. A critical re-appraisal. Eur. J. Clin. Endocrinol. 137: 338, 1997.

    Article  Google Scholar 

  25. Anderson M.S., Bowers C.Y., Kastin A.J., Schalch D.S., Schally A.V., Snyder P.J., Utiger R.D., Wilber J.F., Wise A.J. Synthetic thyrotropin-releasing hormone. A potent stimulator of thyrotropin secretion in man. N. Engl. J. Med. 285: 1279, 1971.

    Article  PubMed  CAS  Google Scholar 

  26. Faglia G., Beck-Peccoz P., Ambrosi B., Ferrari C., Travaglini P. The effects of a synthetic thyotrophin releasing hormone (TRH) in normal and endocrinopathic subjects. Acta Endocrinol (Copenh.) 71: 209, 1972.

    CAS  Google Scholar 

  27. Maeda K., Kato Y., Chinara K., Ohgo S., Iwasaki Y., Imura H. Suppression by thyrotropin-releasing hormone (TRH) of human growth hormone release induced by L-Dopa. J. Clin. Endocrinol. Metab. 41: 408, 1975.

    Article  PubMed  CAS  Google Scholar 

  28. Maeda K., Kato Y., Chihara K., Ohgo S., Iwasaki Y., Abe H., Imura H. Suppression by thyrotropin-releasing hormone (TRH) of growth hormone release induced by arginine and insulin-induced hypoglycemia in man. J. Clin. Endocrinol. Metab. 43: 453, 1976.

    Article  PubMed  CAS  Google Scholar 

  29. Burrow G.N., May P.B., Spaulding S.W., Donabedian R.K. TRH and dopamine interactions affecting pituitary hormone secretion. J. Clin. Endocrinol. Metab. 45: 65, 1977.

    Article  PubMed  CAS  Google Scholar 

  30. Katakami H., Arimura A., Frohman L.A. Hypothalamic somatostatin mediates the suppression of growth hormone secretion by centrally administered thyrotropin-releasing hormone in conscious rats. Endocrinology 117: 1139, 1985.

    Article  PubMed  CAS  Google Scholar 

  31. Harvey S. Thyrotrophin-releasing hormone: a growth hormone-releasing factor. J. Endocrinol. 125: 345, 1990.

    Article  PubMed  CAS  Google Scholar 

  32. Guillaume V., Magnan E., Cataldi M., Dutour A., Sauze N., Renard M., Razafindrabe H., Conte-Devolx B., Deghenghi R., Lenaerts V., Oliver C. GH-releasing hormone secretion is stimulated by a new GH-releasing hexapeptide in sheep. Endocrinology 135: 1073, 1994.

    PubMed  CAS  Google Scholar 

  33. Arvat E., Gianotti L., Grottoli S., Imbimbo B.P., Lenaerts V., Deghenghi R., Camanni F., Ghigo E. Arginine and growth hormone-releasing hormone restore the blunted growth hormone-releasing activity of hexarelin in elderly subjects. J. Clin. Endocrinol. Metab. 79: 1440, 1994.

    PubMed  CAS  Google Scholar 

  34. Goth M.L., Lyons C.E., Canny B.J., Thorner M.O. Pituitary adenylate cyclase activating polypeptide, growth hormone (GH)-releasing peptide and GH-releasing hormone stimulate GH release through distinct pituitary receptors. Endocrinology 130: 939, 1992.

    PubMed  CAS  Google Scholar 

  35. Elias K.A., Ingle G.S., Burnier J.P., Hammonds R.G., McDowell R.S., Rawson T.E., Somers T.C., Stanley M.S., Cronin M. In vitro characterization of four novel classes of growth hormone-releasing peptide. Endocrinology 136: 5694, 1995.

    PubMed  CAS  Google Scholar 

  36. Arvat E., Gianotti L., Divito L., Imbimbo B.P., Lenaerts V., Deghenghi R., Camanni F., Ghigo E. Modulation of growth hormone releasing activity of hexarelin in man. Neuroendocrinology 61: 51, 1995.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Istituto di Scienze Endocrine, Università di Milano, Pad. Granelli, Ospedale Maggiore IRCCS, via F. Sforza 35, 20122, Milano, Italy

    Maura Arosio M.D., G. Casati, O. Biella, S. Porretti & G. Faglia

  2. Mediolanum Farmaceutici S.p.A., Milano, Italy

    B. P. Imbimbo

Authors
  1. Maura Arosio M.D.
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  2. G. Casati
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  3. O. Biella
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  4. S. Porretti
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  5. B. P. Imbimbo
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  6. G. Faglia
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Arosio, M., Casati, G., Biella, O. et al. Lack of effect of hexarelin on TRH-induced TSH response in normal adult man. J Endocrinol Invest 21, 239–244 (1998). https://doi.org/10.1007/BF03347309

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