Abstract
The health and growth of mammalian neonates critically depend on the yield and composition of their mothers’ milk. However, impaired lactogenesis occurs in both women in response to stress and hormonal imbalance and in primiparous sows which exhibit low voluntary feed intake and underdevelopment of mammary tissues. Because of ethical concerns over lactation research with women and children, swine is often used as an animal model to study mammary gland development and the underlying regulatory mechanisms. Available evidence from work with lactating sows shows that amino acids are not only building blocks for protein but are also key regulators of metabolic pathways critical to milk production. Particularly, arginine is the common substrate for the generation of nitric oxide (NO; a major vasodilator and angiogenic factor) and polyamines (key regulators of protein synthesis). Thus, modulation of the arginine-NO pathway may provide a new strategy to enhance the growth (including vascular growth) of mammary tissue and its uptake of nutrients, therefore improving lactation performance in mammals. In support of this proposition, supplementing 0.83% L-arginine (as 1% l-arginine-HCl) or 50 mg/day diethylenetriamine-NO adduct (NO donor) to diets of lactating primiparous sows increased milk production and the growth of suckling piglets. Future studies with animal models (e.g., pigs, sheep, cows, and rats) are necessary to elucidate the underlying mechanisms at molecular, cellular, tissue, and whole-body levels.
Similar content being viewed by others
Abbreviations
- AA:
-
Amino acids
- DETA:
-
Diethylenetriamine-NO adduct
- NO:
-
Nitric oxide
- NRC:
-
National Research Council
References
Boyd RD, Kensinger RS, Harrell RJ, Bauman DE (1995) Nutrient uptake and endocrine regulation of milk synthesis by mammary tissue of lactating sows. J Anim Sci 73(Suppl 2):36–56
Conway M, Hutson SM (2000) Mammalian branched-chain aminotransferases. Methods Enzymol 324:355–365
Dewey KG (2001) Maternal and fetal stress are associated with impaired lactogenesis in humans. J Nutr 131:3012S–3015S
Fang YZ, Yang S, Wu G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18:872–879
Frank JW, Escobar J, Hguyen HV, Jobgen SC, Jobgen WS, Davis TA, Wu G (2007) Oral N-carbamylglutamate supplementation increases protein synthesis in skeletal muscle of piglets. J Nutr 137:315–319
Gabikian P, Clatterbuck RE, Eberhart CG, Tyler BM, Tierney TS, Tamargo RJ (2002) Prevention of experimental cerebral vasospasm by intracranial delivery of a nitric oxide donor from a controlled-release polymer. Stroke 33:2681–2686
Guan X, Bequette BJ, Calder G, Ku PK, Ames KN, Trottier NL (2002) Amino acid availability affects amino acid transport and protein metabolism in the porcine mammary gland. J Nutr 132:1224–1234
Hrabak A, Bajor T, Meszaros G (2008) The inhibitory effect of various indolyl amino acid derivatives on arginase activity in macrophages. Amino Acids 34:293–300
Hrabie JA, Klosie JR, Wink DA (1993) New nitric oxide-releasing zwitterions derived from polyamines. J Org Chem 58:1472–1476
Ji F, Wu G, Blanton JR Jr, Kim SW (2005) Changes in weight and composition in various tissues of pregnant gilts and their nutritional implications. J Anim Sci 83:366–375
Ji F, Hurley WL, Kim SW (2006) Characterization of mammary gland development in pregnant gilts. J Anim Sci 84:579–587
Jobgen WS, Fried SK, Fu WJ, Meininger CJ, Wu G (2006) Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem 17:571–588
Kensinger RS, Collier RJ, Bazer FW (1986) Ultrastructural changes in porcine mammary tissue during lactogenesis. J Anat 145:49–59
Kim SW (1999) Mammary gland growth and nutrient mobilization in lactating sows: a dynamic model to describe nutrient flow. PhD Thesis, University of Illinois at Urbana, Champaign
Kim SW, Wu G (2004) Dietary arginine supplementation enhances the growth of milk-fed young piglets. J Nutr 134:625–630
Kim SW, Hurley WL, Han IK, Stein HH, Easter RA (1999a) Effect of nutrient intake on mammary gland growth in lactating sows. J Anim Sci 77:3304–3315
Kim SW, Hurley WL, Han IK, Easter RA (1999b) Changes in tissue composition associated with mammary gland growth during lactation in the sow. J Anim Sci 77:2510–2516
Kim SW, Osaka I, Hurley WL, Easter RA (1999c) Mammary gland growth as affected by litter size in lactating sows: impact on lysine requirement. J Anim Sci 77:3316–3321
Kim SW, Hurley WL, Han IK, Easter RA (2000) Growth of nursing pigs related to the characteristics of nursed mammary glands. J Anim Sci 78:1313–1318
Kim SW, Easter RA, Hurley WL (2001) Regression of non-suckled mammary glands during lactation in sows as influenced by the stage of lactation, dietary nutrients, and litter size. J Anim Sci 79:2659–2668
Lacasse P, Prosser CG (2003) Mammary blood flow does not limit milk yield in lactating goats. J Dairy Sci 86:2094–2097
Mateo RD, Wu G, Bazer FW, Park JC, Shinzato I, Kim SW (2007) Dietary l-arginine supplementation enhances the reproductive performance of gilts. J Nutr 137:652–656
Mateo RD, Wu G, Moon HK, Carroll JA, Kim SW (2008) Effects of dietary arginine supplementation during gestation and lactation on the performance of lactating primiparous sows and nursing piglets. J Anim Sci 86:827–835
Mejia-Guadarrama CA, Pasquier A, Dourmad JY, Prunier A, Quesnel H (2002) Protein (lysine) restriction in primiparous lactating sows: effects on metabolic state, somatotropic axis, and reproductive performance after weaning. J Anim Sci 80:3286–3300
Meininger CJ, Wu G (2002) Regulation of endothelial cell proliferation by nitric oxide. Methods Enzymol 352:280–295
Miller MR, Megson IL (2007) Recent developments in nitric oxide donor drugs. Br J Pharmacol 151:305–321
Moncada S, Palmer RM, Higgs EA (1989) Biosynthesis of nitric oxide from l-arginine: a pathway for the regulation of cell function and communication. Biochem Pharmacol 38:1709–1715
NRC (1998) Nutrient requirements of swine, 10th edn edn. National Academy Press, Washington, DC
O’Quinn PR, Knabe DA, Wu G (2002) Arginine catabolism in lactating porcine mammary tissue. J Anim Sci 80:467–474
Packer M, Lee W, Kessler PD, Gottlieb SS, Medina N, Yushak M (1987) Prevention and reversal of nitrate tolerance in patients with congestive heart failure. N Engl J Med 317:799–804
Rasmussen KM (2007) Association of maternal obesity before conception with poor lactation performance. Annu Rev Nutr 27:103–121
Renaudeau D, Lebreton Y, Noblet J, Dourmad JY (2002) Measurement of blood flow through the mammary gland in lactating sows: methodological aspects. J Anim Sci 80:196–201
Scherrer U, Sartori C (1997) Insulin as a vascular and sympathoexcitatory hormone: implications for blood pressure regulation, insulin sensitivity and cardiovascular morbidity. Circulation 96:4104–4113
Takano H, Tang XL, Qiu Y, Guo Y, French BA, Bolli R (1998) Nitric oxide donors induce late preconditioning against myocardial stunning and infarction in conscious rabbits via an antioxidant-sensitive mechanism. Circ Res 83:73–84
Trottier NL (1997) Nutritional control of amino acid supply to the mammary gland during lactation in the pig. Proc Nutr Soc 56:581–591
Trottier NL, Shipley CF, Easter RA (1997) Plasma amino acid uptake by the mammary gland of the lactating sow. J Anim Sci 75:1266–1278
Wang JJ, Chen LX, Li DF, Yin YL, Wang XQ, Li P, Dangott LJ, Hu WX, Wu G (2008) Intrauterine growth restriction affects the proteomes of the small intestine, liver and skeletal muscle in newborn pigs. J Nutr 138:60–66
Wu G, Knabe DA (1994) Free and protein-bound amino acids in sow’s colostrum and milk. J Nutr 124:415–424
Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17
Wu G, Meininger CJ (2000) Arginine nutrition and cardiovascular function. J Nutr 130:2626–2669
Wu G, Meininger CJ (2002) Regulation of nitric oxide synthesis by dietary factors. Annu Rev Nutr 22:61–86
Wu G, Bazer FW, Tuo W (1995) Developmental changes of free amino acid concentrations in fetal fluids of pigs. J Nutr 125:2859–2868
Wu G, Knabe DA, Kim SW (2004) Arginine nutrition in neonatal pigs. J Nutr 134:2783S–2390S
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, Collins JK, Perkins-Veazie P, Siddiq M, Dolan KD, Kelly KA, Heaps CL, Meininger CJ (2007a) Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 137:2680–2685
Wu G, Bazer FW, Davis TA, Jaeger LA, Johnson GA, Kim SW, Knabe DA, Meininger CJ, Spencer TE, Yin YL (2007b) Important roles for the arginine family of amino acids in swine nutrition and production. Livest Sci 112:8–22
Zijlstra RT, Whang KY, Easter RA, Odle J (1996) Effect of feeding a milk replacer to early-weaned pigs on growth, body composition, and small intestinal morphology, compared with suckled littermates. J Anim Sci 74:2948–2959
Acknowledgments
This research was supported by funds from North Carolina Agricultural Research Service, Texas AgriLife Research (H-82000), JBS United, and by National Research Initiative Competitive Grant (2008-35206-18764) from the USDA Cooperative State Research, Education, and Extension Service. Our work with sows and piglets was approved by the Texas Tech University and Texas A&M University Animal Care and Use Committees. We thank Ajinomoto Inc. (Tokyo, Japan) for provision of amino acids, our research personnel for technical assistance, as well as Dr. Darrell A. Knabe and Dr. Fengqi Zhou for helpful discussion.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, S.W., Wu, G. Regulatory role for amino acids in mammary gland growth and milk synthesis. Amino Acids 37, 89–95 (2009). https://doi.org/10.1007/s00726-008-0151-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-008-0151-5