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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
Mayer G., Schwinn G. Exercise-induced GH release: suppression by TRH and augmentation by bromocriptine. Acta Endocrinol. (Copenh.) 87 (Suppl. 215): 10, 1978.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Gelato M.C., Merriam G.R. Growth hormone releasing hormone. Annu. Rev. Physiol. 48: 569, 1986.
Tuomisto J., Mannisto P. Neurotransmitter regulation of anterior pituitary hormones. Pharmacol. Rev. 37: 249, 1985.
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.
Zanoboni A., Cucchi R.M., Gibillini M., Zanoboni Muciaccia W. Effect of sulpiride on GHRH-induced GH secretion. Neuroendocrinol. Lett. in press.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Additional information
This work was supported in part by Ministero della Pubblica Istruzione.
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03349071