Abstract
Several factors (including diets, changes in intestinal fluora, and hormones) regulate postnatal intestinal growth and development. Based on the early studies involving modification of the adrenal gland, pituitary gland or hypothalamus, exogenous glucocorticoids and glucocorticoid receptor antagonists are now used to study glucocorticoid-mediated metabolism of amino acids in the small intestine. Findings from these studies indicate that physiological levels of glucocorticoids stimulate the catabolism of glutamine and proline for the synthesis of citrulline and arginine in enterocytes during weaning. In addition, increases in circulating levels of glucocorticoids enhance expression of arginase, proline oxidase and ornithine decarboxylase, as well as polyamine synthesis from arginine and proline in enterocytes. These actions of the hormones promote intestinal maturation and may have therapeutic effects on intestinal disease (e.g., necrotizing enterocolitis). Molecular aspects, species-specific effects, and developmental responsiveness to glucocorticoids should be taken into consideration in designing both experimental and clinical studies.
Similar content being viewed by others
Abbreviations
- ASL:
-
Argininosuccinate lyase
- ASS:
-
Argininosuccinate synthase
- P5C:
-
Pyrroline-5-carboxylate
- P5CS:
-
Pyrroline-5-carboxylate synthase
References
Aragao C, Corte-Real J, Costas B et al (2008) Stress response and changes in amino acid requirements in Senegalese sole (Solea senegalensis Kaup 1858). Amino Acids 34:143–148
Ball RO, Atkinson JL, Bayley HS (1986) Proline as an essential amino acid for the young pig. Br J Nutr 55:659–668
Batt RM, Rutgers HC, Sancak AA (1996) Enteric bacteria: friend or foe? J Small Anim Pract 37:261–267
Bauer CR, Morrison JC, Poole WK et al (1984) A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy. Pediatrics 73:682–688
Burrin DG, Wester TJ, Davis TA et al (1999) Dexamethasone inhibits small intestinal growth via increased protein catabolism in neonatal pigs. Am J Physiol Endocrinol Metab 276:E269–E277
Castillo RO, Glasscock GF, Noren KM, Reisenauer AM (1991) Pituitary regulation of postnatal small intestinal ontogeny in the rat: differential regulation of digestive hydrolase maturation by thyroxine and growth hormone. Endocrinology 129:1417–1423
Chapple RP, Cuaron JA, Easter RA (1989) Response of digestive carbohydrases and growth to graded doses and administration frequency of hydrocortisone and adrenocorticotropic hormone in nursing piglets. J Anim Sci 67:2974–2984
Collington GK, Parker DS, Armstrong DG (1990) The influence of inclusion of either an antibiotic or a probiotic in the diet on the development of digestive enzyme activity in the pig. Br J Nutr 64:59–70
Crowley P, Chalmers I, Keirse MJ (1990) The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 97:11–25
Davis PK, Wu G (1998) Compartmentation and kinetics of urea cycle enzymes in porcine enterocytes. Comp Biochem Physiol B 119:527–537
Deng D, Yin YL, Chu WY et al (2008) Impaired translation initiation activation and reduced protein synthesis in weaned piglets fed a low-protein diet. J Nutr Biochem. doi:10.1016/j.jnutbio.2008.05.014
Dorhout B, van Beusekom CM, Huisman M et al (1996) Estimation of 24-hour polyamine intake from mature human milk. J Pediatr Gastroenterol Nutr 23:298–302
Dugan ME, Knabe DA, Wu G (1995) The induction of citrulline synthesis from glutamine in enterocytes of weaned pigs is not due primarily to age or change in diet. J Nutr 125:2388–2393
Elnif J, Sangild PT (1996) The role of glucocorticoids in the growth of the digestive tract in mink (Mustela vison). Comp Biochem Physiol A 115:37–42
Espinoza J, Hritz A, Kaplan R et al (1975) Regional variation in glycolytic enzyme adaptation to dietary sugars in rat small intestine. Am J Clin Nutr 28:453–458
Espinoza J, Clark SB, Hritz A, Rosensweig NS (1976) Regulation of rat proximal intestinal glycolytic enzyme activity by ileal perfusion with glucose. Gastroenterology 71:295–298
Fan J, Gong XQ, Wu J et al (1994) Effect of glucocorticoid receptor (GR) blockade on endotoxemia in rats. Circ Shock 42:76–82
Ferraris RP (2001) Dietary and developmental regulation of intestinal sugar transport. Biochem J 360:265–276
Flynn NE, Wu G (1996) An important role for endogenous synthesis of arginine in maintaining arginine homeostasis in neonatal pigs. Am J Physiol Regul Integr Comp Physiol 271:R1149–R1155
Flynn NE, Wu G (1997a) Glucocorticoids play an important role in mediating the enhanced metabolism of arginine and glutamine in enterocytes of postweaning pigs. J Nutr 127:732–737
Flynn NE, Wu G (1997b) Enhanced metabolism of arginine and glutamine in enterocytes of cortisol-treated pigs. Am J Physiol Gastrointest Liver Physiol 272:G474–G480
Flynn NE, Meininger CJ, Kelly K et al (1999) Glucocorticoids mediate the enhanced expression of intestinal type II arginase and argininosuccinate lyase in postweaning pigs. J Nutr 129:799–803
Gartner H, Graul MC, Oesterreicher TJ et al (2003) Development of the fetal intestine in mice lacking the glucocorticoid receptor (GR). J Cell Physiol 194:80–87
Grèco S, Niepceron E, Hugueny I et al (2001) Dietary spermidine and spermine participate in the maturation of galactosyltransferase activity and glycoprotein galactosylation in rat small intestine. J Nutr 131:1890–1897
Greene HL, Stifel FB, Hagler L, Herman RH (1975) Comparison of the adaptive changes in disaccharidase, glycolytic enzyme and fructose diphosphatase activities after intravenous and oral glucose in normal men. Am J Clin Nutr 28:1122–1125
Han J, Liu YL, Fan W et al (2008) Dietary l-arginine supplementation alleviates immunosuppression induced by cyclophosphamide in weaned pigs. Amino Acids. doi:10.1007/s00726-008-0184-9
He QH, Kong XF, Wu G et al (2008) Metabolomic analysis of the response of growing pigs to dietary l-arginine supplementation. Amino Acids. doi:10.1007/s00726-008-0192-9
Henning SJ (1978) Plasma concentrations of total and free corticosterone during development in the rat. Am J Physiol Gastrointest Liver Physiol 235:G451–G456
Henning SJ (1981) Postnatal development: coordination of feeding, digestion, and metabolism. Am J Physiol 241:G199–G214
Henning SJ, Oesterreicher TJ, Osterholm DE et al (1999) Meprin mRNA in rat intestine during normal and glucocorticoid-induced maturation: divergent patterns of expression of alpha and beta subunits. FEBS Lett 462:368–372
Hirst M, Feldman D (1982) Glucocorticoid regulation of 1, 25(OH)2vitamin D3 receptors: divergent effects on mouse and rat intestine. Endocrinology 111:1400–1402
Hu CA, Khalil S, Zhaorigetu S et al (2008a) Human Δ1-pyrroline-5-carboxylate synthase: function and regulation. Amino Acids 35:665–672
Hu CA, Williams DB, Zhaorigetu S et al (2008b) Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes. Amino Acids 35:655–664
Imai H, Nakamoto H, Fucshima R et al (2002) Glucocorticoid protects against the development of encapsulating peritoneal sclerosis on peritoneal dialysis. Adv Perit Dial Conf 18:124–130
James PS, Smith MW, Tivey DR, Wilson TJ (1987) Epidermal growth factor selectively increases maltase and sucrase activities in neonatal piglet intestine. J Physiol 393:583–594
Johnson LR (1988) Regulation of gastrointestinal mucosal growth. Physiol Rev 68:456–502
Kahana C (2007) Ubiquitin dependent and independent protein degradation in the regulation of cellular polyamines. Amino Acids 33:225–230
Kiela PR, Guner YS, Xu H et al (2000) Age- and tissue-specific induction of NHE3 by glucocorticoids in the rat small intestine. Am J Physiol Cell Physiol 278:C629–C637
Koldovsky O, Chytil F, Muzcenkova H (1964) Effect of adrenalectomy and diet on the activity of beta-galactosidase in the small intestine during the postnatal development of the rat. Experientia 20:87–89
Koldovsky O, Jumawan J, Palmieri M (1975) Effect of thyroidectomy on the activity of alpha-glucosidases and acid hydrolases in the small intestine of rats during weaning. J Endocrinol 66:31–36
Kornbluth A, Sachar DB (1997) Ulcerative colitis practice guidelines in adults. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 92:204–211
Krane SM (2008) The importance of proline residues in the structure, stability and susceptibility to proteolytic degradation of collagens. Amino Acids 35:703–710
Li P, Yin YL, Li DF et al (2007) Amino acids and immune function. Br J Nutr 98:237–252
Li P, Mai KS, Trushenski J, Wu G (2008a) New developments in fish amino acid nutrition: towards functional and environmentally oriented aquafeeds. Amino Acids. doi:10.1007/s00726-008-0171-1
Li P, Kim SW, Li XL et al (2008b) Dietary supplementation with cholesterol and docosahexaenoic acid affects concentrations of amino acids in tissues of young pigs. Amino Acids. doi:10.1007/s00726-008-0196-5
Liao XH, Majithia A, Huang XL, Kimmel AR (2008) Growth control via TOR kinase signaling, an intracellular sensor of amino acids and energy availability, with crosstalk potential to proline metabolism. Amino Acids 35:761–770
Lin CH, Correia L, Tolia K et al (1998) Early weaning induces jejunal ornithine decarboxylase and cell proliferation in neonatal rats. J Nutr 128:1636–1642
Nanthakumar NN, Henning SJ (1995) Distinguishing normal and glucocorticoid-induced maturation of intestine using bromodeoxyuridine. Am J Physiol Gastrointest Liver Physiol 268:G139–G145
Nanthakumar NN, Young C, Ko JS et al (2005) Glucocorticoid responsiveness in developing human intestine: possible role in prevention of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 288:G85–G92
Orii F, Ashida T, Nomura M et al (2002) Quantitative analysis for human glucocorticoid receptor alpha/beta mRNA in IBD. Biochem Biophys Res Commun 296:1286–1294
Ou DY, Li DF, Cao YH et al (2007) Dietary supplementation with zinc oxide decreases expression of the stem cell factor in the small intestine of weanling pigs. J Nutr Biochem 18:820–826
Patole S (2007) Prevention and treatment of necrotising enterocolitis in preterm neonates. Early Hum Dev 83:635–642
Phang JM, Donald SP, Pandhare J, Liu YM (2008) The metabolism of proline, a stress substrate, modulates carcinogenic pathways. Amino Acids 35:681–690
Ratineau C, Roche C, Chuzel F et al (1996) Regulation of intestinal cholecystokinin gene expression by glucocorticoids. J Endocrinol 151:137–145
Rhoads JM, Niu XM, Surendran S et al (2008) Arginine stimulates intestinal epithelial cell migration via a mechanism requiring both nitric oxide and p70s6k signaling. J Nutr 138:1652–1657
Rider JE, Hacker A, Mackintosh CA et al (2007) Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide. Amino Acids 33:231–240
Sangild PT (1995) Stimulation of gastric proteases in the neonatal pig by a rise in adrenocortical secretion at parturition. Reprod Fertil Dev 7:1293–1298
Sangild PT, Elnif J (1996) Intestinal hydrolytic activity in young mink (Mustela vison) develops slowly postnatally and exhibits late sensitivity to glucocorticoids. J Nutr 126:2061–2068
Silver M, Fowden AL (1989) Pituitary-adrenocortical activity in the fetal pig in the last third of gestation. Q J Exp Physiol 74:197–206
Solomon NS, Gartner H, Oesterreicher TJ, Henning SJ (2001) Development of glucocorticoid-responsiveness in mouse intestine. Pediatr Res 49:782–788
Souba WW, Smith RJ, Wilmore DW (1985) Effects of glucocorticoids on glutamine metabolism in visceral organs. Metabolism 34:450–456
Sugita Y, Takao K, Toyama Y, Shirahata A (2007) Enhancement of intestinal absorption of macromolecules by spermine in rats. Amino Acids 33:253–260
Suryawan A, O’Connor PMJ, Bush JA et al (2008) Differential regulation of protein synthesis by amino acids and insulin in peripheral and visceral tissues of neonatal pigs. Amino Acids. doi:10.1007/s00726-008-0149-z
Takabe S, Mochizuki K, Goda T (2008) De-phosphorylation of GR at Ser203 in nuclei associates with GR nuclear translocation and GLUT5 gene expression in Caco-2 cells. Arch Biochem Biophys 475:1–6
Tan B, Li X, Kong X et al (2008a) Dietary l-arginine supplementation enhances the immune status in early-weaned piglets. Amino Acids. doi:10.1007/s00726-008-0155-1
Tan BE, Yin YL, Liu ZQ et al (2008b) Dietary l-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs. Amino Acids. doi:10.1007/s00726-008-0148-0
Tredger JM, Chhabra RS (1980) Factors affecting the properties of mixed-function oxidases in the liver and small intestine of neonatal rabbits. Drug Metabol Dispos 8:16–22
Wang JY (2007) Polyamines and mRNA stability in regulation of intestinal mucosal growth. Amino Acids 33:241–252
Wang JY, Johnson LR (1990) Gastric and duodenal mucosal ornithine decarboxylase and damage after corticosterone. Am J Physiol 258:G942–G950
Wang W, Qiao S, Li D (2008a) Amino acids and gut function. Amino Acids. doi:10.1007/s00726-008-0152-4
Wang JJ, Wu G, Zhou HJ, Wang FL (2008b) Emerging technologies for amino acid nutrition research in the post-genome era. Amino Acids. doi:10.1007/s00726-008-0193-8
Wang JJ, Chen LX, Li P et al (2008c) Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J Nutr 138:1025–1032
Weigel NL (1996) Steroid hormone receptors and their regulation by phosphorylation. Biochem J 319:657–667
Wu G (1995) Urea synthesis in enterocytes of developing pigs. Biochem J 312:717–723
Wu G (1996) An important role for pentose cycle in the synthesis of citrulline and proline from glutamine in porcine enterocytes. Arch Biochem Biophys 336:224–230
Wu G (1997) Synthesis of citrulline and arginine from proline in enterocytes of postnatal pigs. Am J Physiol Gastrointest Liver Physiol 272:G1382–G1390
Wu G (1998) Intestinal mucosal amino acid catabolism. J Nutr 128:1249–1252
Wu G, Knabe DA (1995) Arginine synthesis in enterocytes of neonatal pigs. Am J Physiol Regul Integr Comp Physiol 269:R621–R629
Wu G, Morris SM (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17
Wu G, Knabe DA, Flynn NE (1994a) Synthesis of citrulline from glutamine in pig enterocytes. Biochem J 299:115–121
Wu G, Borbolla AG, Knabe DA (1994b) The uptake of glutamine and release of arginine, citrulline and proline by the small intestine of developing pigs. J Nutr 124:2437–2444
Wu G, Knabe DA, Flynn NE et al (1996) Arginine degradation in developing porcine enterocytes. Am J Physiol Gastrointest Liver Physiol 271:G913–G919
Wu G, Davis PK, Flynn NE et al (1997) Endogenous synthesis of arginine plays an important role in maintaining arginine homeostasis in postweaning growing pigs. J Nutr 127:2342–2349
Wu G, Flynn NE, Knabe DA (2000a) Enhanced intestinal synthesis of polyamines from proline in cortisol-treated piglets. Am J Physiol Endocrinol Metab 279:E395–E402
Wu G, Flynn NE, Knabe DA, Jaeger LA (2000b) A cortisol surge mediates the enhanced polyamine synthesis in porcine enterocytes during weaning. Am J Physiol Regul Integr Comp Physiol 279:R554–R559
Wu G, Meininger CJ, Kelly K et al (2000c) A cortisol surge mediates the enhanced expression of pig intestinal pyrroline-5-carboxylate synthase during weaning. J Nutr 130:1914–1919
Wu G, Jaeger LA, Bazer FW, Rhoads JM (2004) Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. J Nutr Biochem 15:442–451
Wu G, Bazer FW, Wallace JM, Spencer TE (2006) Intrauterine growth retardation: implications for the animal sciences. J Anim Sci 84:2316–2337
Wu G, Bazer FW, Datta S et al (2008a) Proline metabolism in the conceptus: implications for fetal growth and development. Amino Acids 35:691–702
Wu G, Bazer FW, Datta S et al (2008b) Intrauterine growth retardation in livestock: implications, mechanisms and solutions. Arch Anim Breed 51(special issue 1):4–10
Wu G, Bazer FW, Davis TA et al (2008c) Arginine metabolism and nutrition in growth, health and disease. Amino Acids. doi:10.1007/s00726-008-0210-y
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Flynn, N.E., Bird, J.G. & Guthrie, A.S. Glucocorticoid regulation of amino acid and polyamine metabolism in the small intestine. Amino Acids 37, 123–129 (2009). https://doi.org/10.1007/s00726-008-0206-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-008-0206-7