Abstract
In order to verify the true GH-releasing effect of glucagon and to explain the mechanism underlying this effect, we studied the effect of glucagon (GLU, 1 mg) administered either iv or im on both basal and GHRH (1 μg/kg)- induced GH rise in 48 normal short children and adolescents. Moreover, the in vitro effect of GLU on rat anterior pituitary cells was studied. Intravenous administration of GLU induced no significant GH rise. On the other hand, im GLU administration induced a clearcut GH increase (mean ± SE GH peak after GLU vs placebo = 25.7±3.9 vs 10.1±3.6 μg/L, p<0.01). Intravenous administration of GLU failed to modify the GHRH-induced GH rise either when coadministered with the neurohormone (35.2±4.1 vs 34.1±6.0 μg/L) or when given 60 min earlier (20.2±5.8 vs 21.1±8.3 μg/L). Differently from iv GLU, im GLU strikingly potentiated the GH response to GHRH given 90 min later (57.5±6.3 vs 24.7±9.1 μ/L, p<0.01). Mean plasma glucose levels increased 30 min after GLU, administered either iv or im, and returned to basal levels 60 min later. GH secretion from dispersed rat pituitary cells was unaffected by incubation with GLU (10−10-10−4 mol/L). Incubation of the cells with 10−7 mol/L GHRH induced instead a clear-cut stimulation of GH release. In conclusion, our data demonstrate that glucagon perse has not GH-releasing activity as indicated by its uneffectiveness to release GH in vitro and after intravenous administration. The mechanisms underlying the GH increase which follows intramuscular administration of glucagon are not clear.
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References
Lin T., Tucci J.R. Provocative tests for growth hormone release. A comparison of results with several stimuli. Ann. Intern. Med. 80: 464, 1974.
Roth J., Glick S.M., Yalow R.S., Berson S.A. Hypoglycaemia: a potent stimulus to secretion of growth hormone. Science 140: 987, 1963.
Danforth E., Rosenfeld P.S. Effect of intravenous glucagon on circulating levels of growth hormone and 17-hydroxycorticosteroids. J. Clin. Endocrinol. Metab. 30: 117, 1970.
Cremer G.M., Molnar G.D., Moxness K.E., Shepds S.G., Maker F.T., Jones J.D. Hormonal and biochemical response to glucagon administration in patients with pheochromocytoma and in control subjects. Proc. Staff. Meet. Mayo Clin. 43: 161, 1968.
Milner R.D.G., Wright A.D. Plasma glucose, non-esterified fatty acid, insulin and growth hormone response to glucagon in the newborn. Clin. Sci. 32: 249, 1967.
Cain J.P., Williams G.H., Dluhy R.G. Glucagon stimulation of human growth hormone. J. Clin. Endocrinol. Metab. 31: 222, 1970.
Eddy R.L., Jones L., Hirsh R.M. Effect of exogenous glucagon pituitary polypeptide hormone release. Metabolism 19: 904, 1970.
Weber B., Helge H., Quabbe H.J. Glucagon-induced growth hormone release in children. Acta Endocrinol. (Copenh.) 65: 323, 1970.
AvRuskin T.W., Crigler J.F., Sonksen P.H. Stimulation tests of growth hormone secretion. Rec. Adv. Endocrinol. 238: 395, 1968.
Schofield J.C. Role of cyclic 3′, 5′-adenosine monophosphate in the release of growth hormone in vitro. Nature 215: 1382, 1967.
Valcavi R., Dieguez C., Zini M., Casoli P., Page M.D. Alpha2-adrenergic agonism, arginine and glucagon, release growth hormone through GHRH-independent mechanism in normal human subjects while I-DOPA acts via GHRH. J. Endocrinol. Invest. 11(suppl. 2): 79, 1988 (Abstract).
Parks J.S., Amrhein J.A., Vaidya V., Moshang T., Bongiovanni A.M. Growth hormone response to propranolol-glucagon stimulation: a comparison with other tests of growth hormone reserve. J. Clin. Endocrinol. Metab. 37: 85, 1973.
Mitchell M.L., Suvunrungsi P., Sawin C.T. Effect of propranolol on the response of serum growth hormone to glucagon. J. Clin. Endocrinol. Metab. 32: 470, 1971.
Vandeweghe M., Vermeulen A. Growth hormone and Cortisol secretion after propranolol-glucagon testing in adult. Metabolism 23: 853, 1974.
Ruangwit U., Cavallo A., Fisher J.N., Cliger J.F. Propranolol enhancement of immunoreactive growth hormone (IRGH) response to glucagon in children. Pediatr. Res. 6: 350, 1972.
Colle M., Battin J., Coquelin J.P., Rocchiccioli P. Betaxolol and propranolol in glucagon stimulation of growth hormone. J. Pediatr. 87: 670, 1984.
Delitala G., Frulio T., Pacifico A., Maioli M. Participation of cholinergic muscarinic receptors in glucagon-and arginine-mediated growth hormone secretion in man. J. Clin. Endocrinol. Metab. 55: 1231, 1982.
Krieg R.J., Perkins S.N., Johnson J.H., Rogers J.P., Arimura A., Cronin M.J. Beta-adrenergic stimulation of growth hormone (GH) release in vivo, and subsequent inhibition of GH-releasing factor-induced GH secretion. Endocrinology 122: 531, 1988.
Richardson S.B., Twente S. Inhibition of hypothalamic somatostatin release by adrenergic antagonist. Endocrinology 126: 1043, 1990.
Richardson S.B., Hollander C.S., D’Eletto R., Greenleaf P.W., Thaw C. Acethylcholine inhibits the release of somatostatin from rat hypothalamus in vitro. Endocrinology 107: 122, 1980.
Locatelli V., Torsello A., Redaelli M., Ghigo E., Massara F., Müller E.E. Cholinergic agonist and antagonist drugs modulate the growth hormone response to growth hormone-releasing hormone in the rat: evidence for mediation by somatostatin. J. Endocrinol. 111: 271, 1986.
Podolsky S., Sivaprasad R. Assessment of growth hormone reserve: comparison of intravenous arginine and subcutaneous glucagon stimulation tests. J. Clin. Endocrinol. Metab. 35: 580, 1972.
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Ghigo, E., Bartolotta, E., Imperiale, E. et al. Glucagon stimulates GH secretion after intramuscular but not intravenous administration. Evidence against the assumption that glucagon per se has a GH-releasing activity. J Endocrinol Invest 17, 849–854 (1994). https://doi.org/10.1007/BF03347790
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DOI: https://doi.org/10.1007/BF03347790