Skip to main content
Log in

Inhibitory influence of thyrotropin releasing hormone administration on growth hormone response to low doses of growth hormone-releasing hormone in normal man

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

Abstract

Literature data show that TRH may have either stimulatory or inhibitory actions on GH release according to pathophysiological conditions of the subject. In view of this dual effect of TRH, we studied the possible interaction of TRH and GRF on GH secretion. Six healthy male volunteers received iv in different occasions and in random order: 1 ) GRF 0.05 µg/Kg; 2) GRF 0.1 µg/Kg; 3) GRF 1 µg/Kg; 4) GRF 0.05 µg/Kg + TRH 400 µg, simultaneously; 5) GRF 0.05 µg/Kg + TRH 20 µg, simultaneously; 6) GRF 1 µg/Kg + TRH 400 µg, simultaneously, 7) the vehicle as control treatment. Blood samples were obtained at several time intervals and plasma GH, PRL and TSH were measured by RIA methods. Plasma GH significantly increased in all subjects after all the tested doses of GRF and after the combination of the highest and of the lowest doses of GRF + TRH (treatments 6 and 5). GH responses increased progressively with the dose of GRF administered, even if a clear dose-response relationship could not be demonstrated, owing to the considerable interindividual variability in the responsiveness. The administration of GRF 0.05 µg/Kg increased significantly plasma GH levels vs control treatment. The simultaneous administration of a low effective dose of GRF (0.05 µg/kg) plus a high dose of TRH (400 µg) was able to significantly inhibit the GH secretion elicited by GRF 0.05 µg/Kg alone. The other GRF + TRH combinations tested (treatments 5 and 6) did not modify the GH response to the same doses of GRF given alone. Plasma PRL and TSH did not change either after GRF at any dose or after the vehicle. The combination of GRF with TRH did not modify the normal responses of PRL and TSH to TRH alone. In conclusion, in normal subjects TRH is able to inhibit the GH response to low dose but not to high dose of GRF. These results show another type of interaction between the two hypothalamic hormones; from the practical point of view this interaction casts some doubts on the feasibility of the approach in combined testing of anterior pituitary reserve.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

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

    Article  PubMed  CAS  Google Scholar 

  2. Maeda K., Kato Y., Chihara K., Ohgo S, Iwasaki Y., Imura H. Suppression by thyrotropin releasing hormone of human GH release induced by L-dopa. J. Clin. Endocrinol. Metab. 41: 408, 1975.

    Article  PubMed  CAS  Google Scholar 

  3. Zanoboni A., Zecca L., Zanoboni Muciaccia W. Failure of inhibition by TRH of l-dopa-stimulated GH secretion in patients with alcoholic cirrhosis of the liver. Clin. Endocrinol. (Oxf.) 18: 233, 1983.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Brown P.M., Baccus R., Sachs L., Sonksen P.H., Wheeler M. Bromocriptine suppression of TRH-stimulated prolactin and thyrotrophin release and accompanying inhibition of bromocriptine-induced GH release by TRH in normal man. Clin. Endocrinol. (Oxf.) 10: 481, 1979.

    Article  CAS  Google Scholar 

  6. Zanoboni A., Zanoboni Muciaccia W., Zanussi C., Baraldi R. Suppression of clonidine-induced release of GH by TRH in humans. J. Endocrinol. Invest. 2: 347, 1979.

    Article  PubMed  CAS  Google Scholar 

  7. Mayer G., Schwinn G. Exercise-induced GH release: suppression by TRH and augmentation by bromocriptine. Acta Endocrinol. (Copenh.) 87 (Suppl. 215): 10, 1978.

    Google Scholar 

  8. Chihara K., Kato Y., Maeda K., Abe H., Furumoto M. Imura H. Effects of thyrotropin releasing hormone on sleep and sleep-related growth hormone release in normal subjects. J. Clin. Endocrinol. Metab. 44: 1094, 1977.

    Article  PubMed  CAS  Google Scholar 

  9. Irie M., Tsushima T. Increase of serum growth hormone concentration following TRH injection in patients with acromegaly or gigantism. J. Clin. Endocrinol. Metab. 35: 97, 1972.

    Article  PubMed  CAS  Google Scholar 

  10. Maeda K., Kato Y., Yamaguchi N., Chihara K., Ohgo S., Okanishi Y., Yashimoto Y., Moridera K., Kuromaru S., Imura H. Growth hormone release following TRH injection into patients with anorexia nervosa. Acta Endocrinol. (Copenh.) 87: 1, 1976.

    Google Scholar 

  11. Gonzales-Barcena D., Kastin A.J., Schalcn D.S., Torres-Zamora M., Perez-Pasten E., Kato A., Schally A.V. Responses to thyrotropin releasing hormone in patients with renal failure and after infusion in normal men. J. Clin. Endocrinol. Metab. 36: 117, 1973.

    Article  Google Scholar 

  12. Maeda K., Kato Y., Ohgo S., Chihara K., Yoshimoto Y., Yamaguchi N., Kuromaru S., Imura H. Growth hormone and prolactin release after injection of TRH in patients with depression. J. Clin. Endocrinol. Metab. 40: 501, 1975.

    Article  PubMed  CAS  Google Scholar 

  13. Collu R., Lebeuf G., Letarte J., Ducharme J.R. Increase in plasma growth hormone levels following thyrotropin releasing hormone injection in children with primary hypothyroidism. J. Clin. Endocrinol. Metab. 44: 743, 1977.

    Article  PubMed  CAS  Google Scholar 

  14. Ceda G.P., Speroni G., Dall’Aglio E., Valenti G., Buttunni U. Nonspecific growth hormone responses to thyrotropin- releasing hormone in insulin-dependent diabetes: sex- and age-related pituitary responsiveness. J. Clin. Endocrinol. Metab. 55: 170, 1982.

    Article  PubMed  CAS  Google Scholar 

  15. Zanoboni A., Zanoboni Muciaccia W. Elevated basal growth hormone levels and growth hormone response to TRH in alcoholic patients with cirrhosis. J. Clin. Endocrinol. Metab. 45: 576, 1977.

    Article  PubMed  CAS  Google Scholar 

  16. Knigge U., Thuesen D., Wollesen F., Dejgaard A., Christiansen P.M. Histamine-induced paradoxical growth hormone response to thyrotropin-releasing hormone in normal man. J. Clin. Endocrinol. Metab. 58: 692, 1984.

    Article  PubMed  CAS  Google Scholar 

  17. Zanoboni A, Marinoni S., D’Angelo F., Zanoboni Muciaccia W. TRH does not interfere with growth hormone release induced by GH-RH in normal man. Neuroendocrinol. Lett. 7: 289, 1985.

    CAS  Google Scholar 

  18. Guillemin R., Brazeau P., Bohlen P., Esch F., Ling N., Wehrenberg W.B, Bloch B., Mougin C., Zeytin F., Baird A. Somatocrinin, the growth hormone releasing factor. Recent Prog. Horm. Res. 40: 233, 1984.

    PubMed  CAS  Google Scholar 

  19. Gelato M.C., Pescovitz O.H., Cassorla F., Loriaux D.L, Merriam G.R. Dose-response relationships for the effects of GH releasing factor (1–44)-NH2 in young adult men and women. J. Clin. Endocrinol. Metab. 59: 197, 1984.

    Article  PubMed  CAS  Google Scholar 

  20. Boissel J.P., Cohen R., Biot-Laporte S., Claustrat B., Renard H., Olivier M., Sassolas G. Synthetic human growth hormone releasing factor (h-GRF-1-44-NH2) dose response effect on growth hormone and prolactin secretion in healthy adult men. Eur. J. Clin. Pharmacol. 29: 609, 1986.

    Article  PubMed  CAS  Google Scholar 

  21. Besser G.M., Mortimer C.H. Clinical neuroendocrinology. In: Martini L., Ganong W.F. (eds.), Frontiers in Neuroendocrinology. Raven Press, New York, 1976, p. 227.

    Google Scholar 

  22. Denef C., Maes M., Schramme C. Paracrine interactions in the anterior pituitary: role in the regulation of prolactin and growth hormone secretion. In: Ganong W.F., Martini L. (eds.), Frontiers in Neuroendocrinology. Raven Press, New York, 1986, p. 115.

    Google Scholar 

  23. Jordan V., Dieguez C., Lafaffian I., Rodriguez-Arnao M.D., Gomez-Pan A., Hall R., Scanion M.F. Influence of dopaminergic, adrenargic and cholinergic blockade and TRH administration on GH response to GRF1-29. Clin. Endocrinol. (Oxf.) 24: 291, 1986.

    Article  CAS  Google Scholar 

  24. Giusti M., Lomeo A., Mazzocchi G., Torre R., Monachesi M., Sessarego P., Attanasio R., Giordano G. Effect of simultaneous administration of GHRH (1–40) and TRH on GH, PRL, and TSH secretion in normal man. J. Endocrinol. Invest. 9: 497, 1986.

    Article  PubMed  CAS  Google Scholar 

  25. Tangolo D., Molinatti P., Careddu D., Pogliano G.F., Molinatti G.M. Effect of TRH on GH response to GHRH in normal subjects. J. Endocrinol. Invest. 9 (Suppl. 1): 243, 1986.

    Google Scholar 

  26. Gelato M.C., Merriam G.R. Growth hormone releasing hormone. Annu. Rev. Physiol. 48: 569, 1986.

    Article  PubMed  CAS  Google Scholar 

  27. Tuomisto J., Mannisto P. Neurotransmitter regulation of anterior pituitary hormones. Pharmacol. Rev. 37: 249, 1985.

    PubMed  CAS  Google Scholar 

  28. Spano P.F., Stefanini M., Trabucchi M., Fresia P. Stereospecific interaction of sulpiride with striatal and non-striatal dopamine receptors. In: Spano P.F., Trabucchi M., Corsini G.U., Gessa G.L. (eds.), Sulpiride and other benzamides. Italian Brain Research Found., Milano, 1979, p. 11.

    Google Scholar 

  29. Zanoboni A., Cucchi R.M., Gibillini M., Zanoboni Muciaccia W. Effect of sulpiride on GHRH-induced GH secretion. Neuroendocrinol. Lett. in press.

  30. Chihara K., Kashio Y., Kita T., Okimura Y., Kaji H., Abe H., Fujita T. L-dopa stimulates release of hypothalamic growth hormone-releasing hormone in humans. J. Clin. Endocrinol. Metab. 62: 466, 1986.

    Article  PubMed  CAS  Google Scholar 

  31. Hanew K., Sasaki A., Sato S., Goh M., Yoshinaga K. Growth hormone inhibitory and stimulatory actions of L-dopa in patients with acromegaly. J. Clin. Endocrinol. Metab. 64: 255, 1987.

    Article  PubMed  CAS  Google Scholar 

  32. Collu R., Taché Y. Hormonal effects exerted by TRH through the central nervous system. In: Collu R. (ed.), Central nervous system effects of hypothalamic hormones and other pepides. Raven Press, New York, 1979, p. 97.

    Google Scholar 

  33. Marcovitz S., Goodyer C.G., Guyda H., Gardiner R.J., Hardy J. Comparative study of human fetal, normal adult, and somatotropic adenoma pituitary function in tissue culture. J. Clin. Endocrinol. Metab. 54: 6, 1982.

    Article  PubMed  CAS  Google Scholar 

  34. Looij B.J. jr., Nieuwenhuijzen Kruseman A.C., Mudde A.H., Frolich M., Piaditis G.P., Hodgkinson S.C., McLean C, Grossman A., Coy D.H., Rees L.H., Lowry P.J., Besser G.M. The interaction of growth hormone releasing hormone with other hypothalamic hormones on the release of anterior pituitary hormones. Clin. Endocrinol. (Oxf.) 24: 149, 1986.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported in part by Ministero della Pubblica Istruzione.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zanoboni, A., Gibillini, M., Cucchi, M.R. et al. Inhibitory influence of thyrotropin releasing hormone administration on growth hormone response to low doses of growth hormone-releasing hormone in normal man. J Endocrinol Invest 11, 413–417 (1988). https://doi.org/10.1007/BF03349071

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03349071

Keywords

Navigation