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The negative GH auto-feedback in childhood: Effects of rhGH and/or GHRH on the somatotroph response to GHRH or hexarelin, a peptidyl GH secretagogue, in children

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Abstract

Aim of the present study was to further clarify the negative GH auto-feedback mecha-nisms in childhood. To this goal we studied the effects of rhGH and/or GHRH administration on the GH response to GHRH or hexarelin (HEX), a peptidyl GH secretagogue, in normal short children. In 34 prepubertal children (12 girls and 22 boys, age 8.2- 14.2 yr) with normal short stature (normal height velocity and IGF-I levels) the following tests were performed: group A (no.=11): GHRH (GHRH 1–29, Geref, Serono; 1 μg/kg iv at 150 min) preceded by saline or GHRH at 0 min; group B (no.=6): GHRH preceded by saline or rhGH (0.005 IU/kg iv at 0 min); group C (no.=6): GHRH preceded by rhGH alone or combined with GHRH; group D (no.=6): HEX (2 μg/kg iv at 150 min) alone or pre-ceded by rhGH. In group A, the GH response to GHRH was not modified by pre-treatment with GHRH (GH peak, mean±SEM: 16.7±2.9 vs 15.1±2.3 μg/l, respectively). In group B, the GH response to GHRH was clearly inhibited by rhGH (8.7±2.3 vs 38.8±4.5 μg/l, p<0.001); the GH rise after rhGH in group B overlapped with that after GHRH in group A. In group C, the GH response to GHRH after pre-treatment with rhGH (13.2±4.0 μg/l) was similar to that in group B and was not significantly modified by pre-treatment with rhGH+ GHRH (6.9±2.7 μg/l); the GH rise after rhGH+GHRH was higher (p<0.05) than that after rhGH alone. In group D, the GH response to HEX was significantly blunted by pre-treatment with rhGH (34.1±11.7 vs 51.2±17.9 μg/l, p<0.05). Our results demonstrate that in childhood the somatotroph response to GHRH is preserved after GHRH while it is inhibited after rhGH administration, which is also able to blunt the GH response to HEX. Thus, the somatostatin-mediated negative GH autofeedback is already operative in childhood; the reason why the GHRH-induced GH rise is not inhibited by GHRH pre-treatment is unexplained.

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References

  1. Muller E.E., Nisticò G. Neurotransmitter regulation of the anterior pituitary. In: Muller E.E., Nisticò G. (Eds.), Brain messenger and the pituitary. Academic Press, San Diego, 1989, pp. 404–537.

    Google Scholar 

  2. Ghigo E. Neurotransmitter control of growth hormone secretion. In: de la Cruz L.F. (Eds.), Regulation of growth hormone and somatic growth. Excerpta Medica, Amsterdam, 1992, pp. 103–136.

    Google Scholar 

  3. Hartman M.L., Veldhuis J.D., Thomer M.O. Normal control of growth hormone secretion. Horm. Res. 1993, 40: 37–47.

    Article  CAS  PubMed  Google Scholar 

  4. Tannenbaum G.S. Evidence for autoregulation of growth hormone secretion via the central nervous system. Endocrinology 1980, 107: 2117–2120.

    Article  CAS  PubMed  Google Scholar 

  5. Torsello A., Panzeri G., Cermenati P., Caroleo M.C., Ghigo E., Camanni F., Muller E.E., Locatelli V. Involvement of the somatostatin and cholinergic systems in the mechanism of growth hormone autofeedback regulation in the rat. J. Endocrinol. 1988, 117: 273–281.

    Article  CAS  PubMed  Google Scholar 

  6. Lanzi R., Tannenbaurn G.S. Time-dependent reduction and potentiation of growth hormone (GH) responsiveness to GH-releasing factor induced by exogenous GH: role for somatostatin. Endocrinology 1992, 130: 1822–1828.

    CAS  PubMed  Google Scholar 

  7. Ross R.J.M., Tsagarakis S., Grossman A., Nhagafoong L., Touzel R.J., Rees L.H., Besser G.M. GH feedback occurs through modulation of hypo-thalamic somatostatin under cholinergic control: studies with pyridostigmine and GHRH. Clin. Endocrinol. (Oxf.) 1987, 27: 727–733.

    Article  CAS  Google Scholar 

  8. Massara F., Ghigo E., Molinatti P., Mazza E., Locatelli V., Molinatti G.M., Muller E.E., Camanni F. Potentiation of cholinergic tone by pyridostigmine bromide reinstates and potentiates the growth hormone responsiveness to intermittent administration of growth hormone-releasing factor in man. Acta Endocrinol. 1986, 113: 12–16.

    CAS  PubMed  Google Scholar 

  9. Kelijman M., Frohman L. β adrenergic modulation of growth hormone (GH) autofeedback on sleep-associated and pharmacologically induced GH secretion. J. Clin. Endocrinol. Metab. 1989, 69: 1187–1194.

    Article  CAS  PubMed  Google Scholar 

  10. Arosio M., Losa M., Bazzoni N., Bochicchio D., Palmieri E., Nava C., Faglia G. Effects of propranolol on GH responsiveness to repeated GH-releasing hormone stimulation in normal subjects. Acta Endocrinol. (Copenh.) 1990, 122: 135–139.

    Google Scholar 

  11. Ghigo E., Arvat E., Valente F., Nicolosi M., Boffano G.M., Procopio M., Bellone J., Maccario M., Mazza E., Camanni F. Arginine reinstates the somatotrope responsiveness to intermittent growth hormone-releasing hormone administration in normal adults. Neuroendocrinology 1991, 54: 291–294.

    Article  CAS  PubMed  Google Scholar 

  12. Arvat E., Ghigo E., Nicolosi M., Boffano G.M., Bellone J., Yin-Zhang W., Mazza E., Camanni F. Galanin reinstates the growth hormone response to repeated growth hormone-releasing hormone administration in man. Clin. Endocrinol. (Oxf.) 1992, 35: 347–350.

    Article  Google Scholar 

  13. Ghigo E., Goffi S., Mazza E., Arvat E., Procopio M., Bellone J., Muller E., Camanni F. Repeated GH-releasing hormone administration unravels different GH secretory patterns in normal adults and children. Acta Endocrinol. (Copenh.) 1989, 120: 598–601.

    CAS  Google Scholar 

  14. Ghigo E., Arvat E., Goffi S., Bellone J., Valente F., Procopio M., Ghigo M.C., Camanni F. Repetitive GHRH and arginine administration to explore the maximal secretory capacity of somatotroph cells during lifespan. Exp. Clin. Endocrinol. (Life Sci. Adv.) 1991, 10: 191–198.

    Google Scholar 

  15. Sartorio A., Spada A., Morabito F., Faglia G. Different GH responsiveness to repeated GHRH administration in normal children and adults. J. Endocrinol. Invest. 1988, 11: 727–729.

    CAS  PubMed  Google Scholar 

  16. Corpas E., Harman S.M., Blackman M.R. Human growth hormone and human aging. Endocr. Rev. 1993, 14: 20–39.

    Article  CAS  PubMed  Google Scholar 

  17. Ghigo E., Arvat E., Gianotti L., Ramunni J., Di Vito L., Maccagno B., Grottoli S., Camanni F. Human aging and the GH-IGF-I axis. J. Ped. Endocrinol. Metab. 1996, 9: 271–278.

    Google Scholar 

  18. Muller E.E., Cella S.G., Parenti M., Deghenghi R., Locatelli V., De Gennaro Colonna V., Torsello A., Cocchi D. Somatotropic dysregulation in old mammals. Horm. Res. 1995, 43: 39–45.

    Article  CAS  PubMed  Google Scholar 

  19. Bellone J., Aimaretti G., Valetto M.R., Bellone S., Baffoni C., Arvat E., Seminara S., Camanni F., Ghigo E. Acute administration of recombinant human growth hormone inhibits the somatotrope responsiveness to growth hormone-releasing hormone in childhood. Eur. J. Endocrinol. 1996, 135: 421–424.

    Article  CAS  PubMed  Google Scholar 

  20. Mouhieddine O.E.B., Levy L., Benlot C., Peillon F., Joubert D. Growth hormone (GH)-releasing hormone tonically inhibits in vitro endogenous somatostatin in human GH-secreting tumors. J. Clin. Endocrinol. Metab. 1995, 80: 1691–1695.

    CAS  PubMed  Google Scholar 

  21. Ghigo E., Arvat E., Muccioli G., Camanni F. Growth hormone-releasing peptides. Eur. J. Endocrinol. 1997, 136: 445–460.

    Article  CAS  PubMed  Google Scholar 

  22. Bowers C.Y., Veeraragavan K., Sethumadhavan K. Atypical growth hormone releasing peptides. In: Bercu B.B., Walker R.F. (Eds.), Growth hormone II: basic and clinical aspects. New York, Springer Verlag, 1993, pp. 203–222.

    Google Scholar 

  23. Smith R.G., Cheng K., Schoen W.R., Pong S.S., Hickey G., Jacks T., Butler B., Chan W.W.S., Chaung L.Y.P., Judith F., Taylor J., Shoen W.R., Wyvratt M.J., Fisher M.H. A non-peptidyl GH segretagogue. Science 1993, 260: 1640–1643.

    Article  CAS  PubMed  Google Scholar 

  24. Casanueva F.F., Dieguez C. Growth hormone segretagogues: Physiological role and clinical utility. Trends Endocrinol. Metab. 1999, 10: 30–38.

    Article  CAS  PubMed  Google Scholar 

  25. Rosenthal S.M., Kaplan S.L, Grumbach M.M. Short term continuous intravenous infusion of growth hormone (GH) inhibits GH-releasing hormone-induced GH secretion: a time-dependent effect. J. Clin. Endocrinol. Metab. 1989, 68: 1101–1105.

    Article  CAS  PubMed  Google Scholar 

  26. Pontiroli A.E., Lanzi R., Pozza G. Inhibition of the growth hormone (GH) response to GH-releasing hormone by constant met-GH infusions. J. Clin. Endocrinol. Metab. 1989, 68: 956–959.

    Article  CAS  PubMed  Google Scholar 

  27. Arvat E., Di Vito L., Gianotti L., Ramunni J., Boghen M.F., Deghenghi R., Camanni F., Ghigo E. Mechanism underlying the negative growth hormone (GH) autofeedback on the GH-releasing effect of Hexarelin in man. Metabolism 1997, 46: 83–88.

    Article  CAS  PubMed  Google Scholar 

  28. Rosenbaum M., Loche S., BaIzano S., Gertner J.M. Short-term Met-hGH infusion inhibits somatotroph response to growth hormone releasing hormone (1–44). Metabolism 1988, 37: 131–135.

    Article  CAS  PubMed  Google Scholar 

  29. Weherenberg W.B., Brazeau P., Ling N., Textore G., Guillemin R. Pituitary growth hormone response in rats during a 24-hour infusion of growth hormone-releasing factor. Endocrinology 1984, 114: 1613–1619.

    Article  Google Scholar 

  30. Ghigo E., Arvat E., Camanni F. Growth hormone segretagogues as corticotro-phin-releasing factors. Growth Hormone and IGF-I Research 1998, 8: 145–148.

    Article  CAS  Google Scholar 

  31. Massoud A.T., Hindmarsh P.C., Brook C.G.D. Hexarelin induced growth hormone release is influenced by exogenous growth hormone. Clin. Endocrinol. 1995, 43: 617–621.

    Article  CAS  Google Scholar 

  32. 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 1995, 44: 1134–1138.

    Article  Google Scholar 

  33. Arvat E., Gianotti L., Ramunni J., Di Vito L., Deghenghi R., Camanni F., Ghigo E. Influence of beta-adrenergic agonists and antagonists on the GH-releasing effect of Hexarelin in man. J. Endocrinol. Invest. 1996, 19: 25–29.

    CAS  PubMed  Google Scholar 

  34. Arvat E., Maccagno B., Ramunni J., Gianotti L., Di Vito L., Deghenghi R., Camanni F., Ghigo E. Effects of histaminergic antagonists on the GH-releasing activity of GHRH or hexarelin, a synthetic hexapeptide, in man. J. Endocrinol. Invest. 1997, 20: 122–127.

    CAS  PubMed  Google Scholar 

  35. Arvat J., Maccagno B., Ramunni J., Broglio F., Lanfranco F., Giordano R., Benso A., Deghenghi R., Ghigo E. Influence of galanin and serotonin on the endocrine response to hexarelin, a synthetic peptidyl GH sec-retagogue, in normal women. J. Endocrinol. Invest. 1998, 21: 673–679.

    CAS  PubMed  Google Scholar 

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Correspondence to Ezio Ghigo.

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Bellone, J., Bellone, S., Aimaretti, G. et al. The negative GH auto-feedback in childhood: Effects of rhGH and/or GHRH on the somatotroph response to GHRH or hexarelin, a peptidyl GH secretagogue, in children. J Endocrinol Invest 23, 158–162 (2000). https://doi.org/10.1007/BF03343699

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