© Freund Publishing House Ltd., London Journal of Pediatric Endocrinology & Metabolism, 9, 523-531 (1996) Effects of Phenylalanine, Histidine, and Leucine on Basal and GHRH-stimulated GH Secretion and on PRL, Insulin, and Glucose Levels in Short Children. Comparison with the Effects of Arginine J. Bellone 1 , M.R Valetto 1 , G. Aimaretti 1 , M. Segni 2 , C. Volta 3 , G. Cardinale 4 , C. Baffoni 1 , A.M. Pasquino 2 , S. Bernasconi 3 , E. Bartolotta 4 , M. Mucci 5 and E. Ghigo 1 'Division of Endocrinology, Department of Internal Medicine, University of Turin; 2 Division of Pediatrics, University of Rome; 3 Division of Pediatrics, University of Parma; 4 Division of Pediatrics, Hospital of Recanati, Macerata; 5 Pharmacia PH, Milan; Italy ABSTRACT Of the amino acids arginine is the most potent GH secretagogue in man. It potentiates the GH response to GHRH, exerts a weaker PRL-releasing effect, stimulates insulin and glucagon and induces a biphasic glucose varia- tion. The potency and effects of other amino acids on pituitary and pancreatic hormones need to be clarified. In 43 children with normal short stature (5.3-14.0 yr; 30 Μ and 13 F) the effects of the infusion of phenylalanine (Phe, 0.08 g/kg), histidine (His, 0.1 g/kg), and leucine (Leu, 0.08 g/kg) on basal and GHRH-stimulated GH secretion and on PRL, insulin and glucose levels were studied and compared with those of arginine at high (hArg, 0.5 g/kg) or low dose (lArg, 0.2 g/kg). Phe increased basal (p<0.05) but not GHRH-stimulated GH levels, induced PRL and insulin rises (p<0.03 and p<0.03), and did not change glycemia. Though a trend toward an increase in basal GH levels was found after His, His and Leu did not significantly modify either basal or GHRH-induced GH secretion nor basal PRL, insulin and glucose levels. Both hArg and lArg increased basal (p< Reprint address: E. Ghigo, M.D. Divisione di Endocrinologia Ospedale Molinette C.so Dogliotti 14 10126 Torino, Italy 0.0001 and p<0.05, respectively) and GHRH- stimulated GH levels (p<0.006 and p<0.006). hArg increased both PRL (p<0.002) and insulin levels (p<0.005) more (p<0.0005 and p<0.004) than lArg (p<0.005 and p<0.005), while glucose levels showed a similar increase followed by a similar decrease. We conclude that in childhood: a) Phe significantly increases GH secretion but, differently from Arg, does not potentiate the response to GHRH, suggesting different mecha- nisms of action of these amino acids; b) differ- ently from His and Leu, Phe is a PRL and insu- lin secretagogue but is less potent than Arg; c) Arg has the highest stimulatory effect on pitui- tary and pancreatic hormones. KEY WORDS GH, PRL, insulin, glucose, phenylalanine, histidine, leucine, arginine INTRODUCTION Somatotrope secretion is mainly regulated by the interaction of two hypophysiotropic neurohor- mones, GHRH, which stimulates GH synthesis and release, and somatostatin, which inhibits hormone release /1,2/. Several other neurotransmitters and neuropeptides have important influences on GH release, generally acting via modulation of GHRH and/or somatostatin release /1,2/. Amino acids, acting either as metabolic inputs or neurotransmit- VOLUME 9, NO. 5, 1996 523 Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 6/30/15 8:53 PM