Neuroendocrine Control of Growth Hormone Secretion, EUGENIO E. MULLER, VITTORIO LOCATELLI, AND DANIELA COCCHI,
PHYSIOLOGICAL REVIEWS Vol. 79, No. 2, April 1999
Amino acids are a potent stimulus for GH secretion, either as selected nutrients or when included in a proteinrich meal (99, 283, 516). Parenteral administration of an amino acid solution raises GH secretion by acting on pulsatility and pulse amplitude, an effect presumably mediated by increased GHRH secretion (791).
Arginine is the most striking stimulant, although lysine, ornithine, tyrosine, glycine, and tryptophan are all effective GH releasers (564). An oral mixture of arginine and lysine evokes a sevenfold increase of plasma GH levels (516), and a similar effect is observed after arginine aspartate (99, 163). Arginine-induced GH secretion in humans is blocked by antagonists of a-adrenergic and cholinergic neurotransmission (153, 178), a carbohydrate-rich diet (710), hyperglycemia (711) and NEFA, anti-E2 (878). Estrogens enhance arginine-induced GH secretion in men or women (711).
The effect of arginine on GH secretion appears to be exerted through suppression of hypothalamic SS release, as suggested by neuropharmacological studies (22, 413, 414). Alternatively, the effect of arginine on GH and other pituitary hormones (56, 366) may depend on its conversion to NO, a gaseous neurotransmitter (734). Arginine is in fact a more effective GH releaser than muscarinic cholinergic agonists (414) which inhibit SS release (629). ...L-arginine is a potent GH secretagogue in humans (711); however, its effect does not appear to be linked to NO production...
REFERENCES:
22. ALBA-ROTH, J., A. O. MULLER, J. SCHOPOL, AND K. VON WERDER. Arginine: stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J. Clin. Endocrinol. Metab. 67: 1186–1189, 1988.
56. ASSAN, R., G. ROSSELIN, AND J. DOLAIS. Effects sur la glucagonemie des perfusions et ingestions d’acides amines. J. Ann. Diabetol. Hotel Dieu. Ed. Medicales 7: 25–41, 1967
99. BESSET, A., A. BONARDET, G. RAUDONIN, B. DESCOMPS, AND P. PASSNANT. Increase in sleep-related GH and Prl secretion after chronic arginine aspartate administration in man. Acta Endocrinol. 99: 18–23, 1982.
153. BUCKLER, J. H. M., A. M. BOLD, M. TABERNER, AND D. R. LONDON. Modification of hormonal responses to arginine by adrenergic blockade. Br. Med. J. 3: 153–154, 1969.
163. CAMPISTRON, G. Approache Pharmacologique de l’Arginine et de l’Acide Aspartique. Etude Pharmacocinetique e Pharmacodinamique (PhD thesis). Toulouse, France: Faculte` des Sciences Pharmacocinetique, 1980, no. 112.
178. CASANUEVA, F. F., L. VILLANUEVA, J. A. CABRANES, J. CABEZAS- CERRATO, AND A. FERNANDO-CRUZ. Cholinergic mediation of growth hormone secretion elicited by arginine, clonidine and physical exercise in man. J. Clin. Endocrinol. Metab. 59: 526–530, 1984.
283. DAUGHADAY, W. H. Growth hormone: normal synthesis, secretion, control and mechanisms of action. In: Endocrinology, edited by L. J. De Groot. Philadelphia, PA: Saunders, 1989, vol. 1, p. 318–329.
366. FLOYD, J. C., JR., S. S. FAJANS, J. W. CONN, R. F. KNOPF, AND J. A. RULL. Stimulation of insulin secretion by amino acids. J. Clin. Invest. 45: 1487–1502, 1966.
413. GHIGO, E., S. GOFFI, E. ARVAT, M. NICOLOSI, M. PROCOPIO, J. BELLONE, E. IMPERIALE, E. MAZZA, G. BARACCHI, AND F. CAMANNI. Pyridostigmine partially restores the GH responsiveness to GHRH in normal aging. Acta Endocrinol. 123: 169–174, 1990.
414. GHIGO, E., S. GOFFI, M. NICOLOSI, E. ARVAT, J. BELLONE, M. PROCOPIO, F. VALENTE, E. MAZZA, M. C. GHIGO, AND F. CAMANNI. Growth hormone responsiveness to combined administration of arginine and GH-releasing hormone does not vary with age in man. J. Clin. Endocrinol. Metab. 71: 1481–1485, 1990
564. KNOPF, R. F., J. W. CONN, S. S. FAJANS, J. A. RULL, E. M. GUNTSCHE, AND C. A. THIFFAULT. The normal endocrine response to ingestion of protein and infusion of amino acids. Sequential secretion of insulin and growth hormone. Trans. Assoc. Am. Phys. 79: 312–321, 1966.
516. ISIDORI, A., A. LOMONACO, AND M. CAPPA. A study of growth hormone release in man after oral administration of amino acids. Curr. Med. Res. Opin. 7: 475–481, 1981.
629. LOCATELLI, V., A. TORSELLO, M. REDAELLI, E. GHIGO, F. MASSARA, AND E. E. MU¨ LLER. 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: 271–278, 1986.
710. MERIMEE, T. J. Growth hormone: secretion and action. In: Endocrinology, edited by L. De Groot. New York: Grune & Stratton, 1980, p. 123–132.
711. MERIMEE, T. J., D. RABINOWITZ, AND S. E. FINEBERG. Arginine initiated release of human growth hormone: factors modifying the response in normal man. N. Engl. J. Med. 280: 1434–1438, 1969.
734. MONCADA, S., R. M. J. PALMER, AND E. A. HIGGS. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol. Rev. 43: 109–142, 1991.
791. OKADA, K., H. SUGIHARA, S. MINAMI, AND I. WAKABAYASHI. Effect of parenteral administration of selected nutrients and central injection of g-globulin from antiserum to neuropeptide Y on growth hormone secretory pattern in food-deprived rats. Neuroendocrinology 57: 678–686, 1993.
878. REFETOFF, S., P. H. FRANK, C. ROUBEBUSH, AND L. J. DE GROOT. Evaluation of pituitary function. In: Endocrinology, edited by L. J. De Groot. New York: Grune & Stratton, 1979, p. 175–190.