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Optimizing hormonal and amino acid combinations for enhanced cell proliferation and cell cycle progression in bovine mammary epithelial cells

  • Hyuk Cheol Kwon (Department of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Hyun Su Jung (Department of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Do Hyun Kim (Department of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Jong Hyeon Han (Department of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Seo Gu Han (Department of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Dong Hyun Keum (Department of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Seong Joon Hong (Department of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Sung Gu Han (Department of Food Science and Biotechnology of Animal Resources, Konkuk University)
  • Received : 2023.05.25
  • Accepted : 2023.08.11
  • Published : 2023.11.01

Abstract

Objective: The number of bovine mammary epithelial cells (BMECs) is closely associated with the quantity of milk production in dairy cows; however, the optimal levels and the combined effects of hormones and essential amino acids (EAAs) on cell proliferation are not completely understood. Thus, the purpose of this study was to determine the optimal combination of individual hormones and EAAs for cell proliferation and related signaling pathways in BMECs. Methods: Immortalized BMECs (MAC-T) were treated with six hormones (insulin, cortisol, progesterone, estrone, 17β-estradiol, and epidermal growth factor) and ten EAAs (arginine, histidine, leucine, isoleucine, threonine, tryptophan, lysine, methionine, phenylalanine, and valine) for 24 h. Results: Cells were cultured in a medium containing 10% fetal bovine serum (FBS) as FBS supplemented at a concentration of 10% to 50% showed a comparable increase in cell proliferation rate. The optimized combination of four hormones (insulin, cortisol, progesterone, and 17β-estradiol) and 20% of a mixture of ten EAAs led to the highest cell proliferation rate, which led to a significant increase in cell cycle progression at the S and G2/M phases, in the protein levels of proliferating cell nuclear antigen and cyclin B1, cell nucleus staining, and in cell numbers. Conclusion: The optimal combination of hormones and EAAs increased BMEC proliferation by enhancing cell cycle progression in the S and G/2M phases. Our findings indicate that optimizing hormone and amino acid levels has the potential to enhance milk production, both in cell culture settings by promoting increased cell numbers, and in dairy cows by regulating feed intake.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2022R1A2C1008327).

References

  1. Macias H, Hinck L. Mammary gland development. Wiley Interdiscip Rev Dev Biol 2012;1:533-57. https://doi.org/10.1002/wdev.35
  2. Capuco AV, Choudhary RK. Symposium review. Determinants of milk production: Understanding population dynamics in the bovine mammary epithelium. J Dairy Sci 2020;103:2928-40. https://doi.org/10.3168/jds.2019-17241
  3. Bidereac C, Petroman C, Stefanovic M, Petroman I, Marin D. Study on the factors influencing cow milk production in dairy cows. Lucrari stiintifice Manag Agricol 2014;16:202-5.
  4. Silanikove N, Shamay A, Shinder D, Moran A. Stress down regulates milk yield in cows by plasmin induced β-casein product that blocks K+ channels on the apical membranes. Life Sci 2000;67:2201-12. https://doi.org/10.1016/S0024-3205(00)00808-0
  5. Zhu D, Kebede B, McComb K, Hayman A, Chen G, Frew R. Milk biomarkers in relation to inherent and external factors based on metabolomics. Trends Food Sci Technol 2021;109:51-64. https://doi.org/10.1016/j.tifs.2020.12.012
  6. Chen B, Grandison AS, Lewis MJ. Best use for milk-A review. II-Effect of physiological, husbandry and seasonal factors on the physicochemical properties of bovine milk. Int J Dairy Technol 2017;70:155-64. https://doi.org/10.1111/1471-0307.12355
  7. Jaswal S, Jena MK, Anand V, et al. Critical review on physiological and molecular features during bovine mammary gland development: recent advances. Cells 2022;11:3325. https://doi.org/10.3390/cells11203325
  8. Borellini F, Oka T. Growth control and differentiation in mammary epithelial cells. Environ Health Perspect 1989;80:85-99. https://doi.org/10.1289/ehp.898085
  9. Baumrucker CR, Stemberger BH. Insulin and insulin-like growth factor-I stimulate DNA synthesis in bovine mammary tissue in vitro. J Anim Sci 1989;67:3503-14. https://doi.org/10.2527/jas1989.67123503x
  10. Hannan FM, Elajnaf T, Vandenberg LN, Kennedy SH, Thakker RV. Hormonal regulation of mammary gland development and lactation. Nat Rev Endocrinol 2023;19:46-61. https://doi.org/10.1038/s41574-022-00742-y
  11. Joshi PA, Jackson HW, Beristain AG, et al. Progesterone induces adult mammary stem cell expansion. Nature 2010;465:803-7. https://doi.org/10.1038/nature09091
  12. Capuco AV, Akers RM. Management and environmental influences on mammary gland development and milk production. In: Greenwood P, Bell A, Vercoe P, Viljoen G, editors. Managing the prenatal environment to enhance livestock productivity. Dordrecht, The Netherland: Springer; 2009. pp. 259-92. https://doi.org/10.1007/978-90-481-3135-8_9
  13. Rezaei R, Wu Z, Hou Y, Bazer FW, Wu G. Amino acids and mammary gland development: nutritional implications for milk production and neonatal growth. J Anim Sci Biotechnol 2016;7:20. https://doi.org/10.1186/s40104-016-0078-8
  14. Dai W, White R, Liu J, Liu H. Seryl-tRNA synthetase-mediated essential amino acids regulate β-casein synthesis via cell proliferation and mammalian target of rapamycin (mTOR) signaling pathway in bovine mammary epithelial cells. J Dairy Sci 2018;101:10456-68. https://doi.org/10.3168/jds.2018-14568
  15. Ge Y, Li F, He Y, et al. L-arginine stimulates the proliferation of mouse mammary epithelial cells and the development of mammary gland in pubertal mice by activating the GPRC6A/PI3K/AKT/mTOR signalling pathway. J Anim Physiol Anim Nutr 2022;106:1383-95. https://doi.org/10.1111/jpn.13730
  16. Qi H, Meng C, Jin X, Li X, Li P, Gao X. Methionine promotes milk protein and fat synthesis and cell proliferation via the SNAT2-PI3K signaling pathway in bovine mammary epithelial cells. J Agric Food Chem 2018;66:11027-33. https://doi.org/10.1021/acs.jafc.8b04241
  17. Rios AC, Fu NY, Jamieson PR, et al. Essential role for a novel population of binucleated mammary epithelial cells in lactation. Nat Commun 2016;7:11400. https://doi.org/10.1038/ncomms11400
  18. Murney R, Stelwagen K, Wheeler TT, Margerison JK, Singh K. The effects of milking frequency in early lactation on milk yield, mammary cell turnover, and secretory activity in grazing dairy cows. J Dairy Sci 2015;98:305-11. https://doi.org/10.3168/jds.2014-8745
  19. Geiger A. The pre-pubertal bovine mammary gland: unlocking the potential of the future herd. Animal 2019;13(Suppl 1):s4-10. https://doi.org/10.1017/S1751731119001204
  20. Boutinaud M, Guinard-Flament J, Jammes H. The number and activity of mammary epithelial cells, determining factors for milk production. Reprod Nutr Dev 2004;44:499-508. https://doi.org/10.1051/rnd:2004054
  21. Akers RM. Endocrine, growth factor, and neural regulation of mammary function. In: Akers RM, editor. Lactation and the mammary gland. Ames, IA, USA: Blackwell Publishing Company; 2016. pp. 165-98. https://doi.org/10.1002/9781119264880.ch7
  22. Hosios AM, Hecht VC, Danai LV, et al. Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells. Dev Cell 2016;36:540-9. https://doi.org/10.1016/j.devcel.2016.02.012
  23. Cai J, Wang D, Liu J. Regulation of fluid flow through the mammary gland of dairy cows and its effect on milk production: a systematic review. J Sci Food Agric 2018;98:1261-70. https://doi.org/10.1002/jsfa.8605
  24. Brickell JS, McGowan MM, Wathes DC. Effect of management factors and blood metabolites during the rearing period on growth in dairy heifers on UK farms. Domest Anim Endocrinol 2009;36:67-81. https://doi.org/10.1016/j.domaniend.2008.10.005
  25. Bionaz M, Loor JJ. Gene networks driving bovine mammary protein synthesis during the lactation cycle. Bioinform Biol Insights 2011;5:BBI-S7003. https://doi.org/10.4137/BBI.S7003
  26. Mukherjee J, Mallick S, Chaudhury M, Prakash BS, Dang AK. Infradian rhythmicity in milk leukocyte activity together with plasma cortisol and prolactin levels throughout the lactation period in high-yielding crossbred cows. Biol Rhythm Res 2015;46:909-17. https://doi.org/10.1080/09291016.2015.1066544
  27. Fustini M, Galeati G, Gabai G, et al. Overstocking dairy cows during the dry period affects dehydroepiandrosterone and cortisol secretion. J Dairy Sci 2017;100:620-8. https://doi.org/10.3168/jds.2016-11293
  28. Kamada H. Effects of selenium-rich yeast supplementation on the plasma progesterone levels of postpartum dairy cows. Asian-Australas J Anim Sci 2017;30:347-54. https://doi.org/10.5713/ajas.16.0372
  29. Erb RE, Chew BP, Keller HF. Relative concentration of extrogen and progestrone in milk and blood, and excretion of estrogene in urine. J Anim Sci 1977;45:617-26. https://doi.org/10.2527/jas1977.453617x
  30. Kobayashi K, Oyama S, Kuki C, et al. Distinct roles of prolactin, epidermal growth factor, and glucocorticoids in β-casein secretion pathway in lactating mammary epithelial cells. Mol Cell Endocrinol 2017;440:16-24. https://doi.org/10.1016/j.mce.2016.11.006
  31. Wang T, Jin J, Qian C, et al. Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment. Cancer Cell Int 2021;21:295. https://doi.org/10.1186/s12935-021-02003-w
  32. Yang XR, Pfeiffer RM, Garcia-Closas M, et al. Hormonal markers in breast cancer: coexpression, relationship with pathologic characteristics, and risk factor associations in a population-based study. Cancer Res 2007;67:10608-17. https://doi.org/10.1158/0008-5472.CAN-07-2142
  33. Kim SW, Wu G. Regulatory role for amino acids in mammary gland growth and milk synthesis. Amino Acids 2009;37:89-95. https://doi.org/10.1007/s00726-008-0151-5
  34. Gao HN, Zhao SG, Zheng N, et al. Combination of histidine, lysine, methionine, and leucine promotes β-casein synthesis via the mechanistic target of rapamycin signaling pathway in bovine mammary epithelial cells. J Dairy Sci 2017;100:7696-709. https://doi.org/10.3168/jds.2015-10729
  35. Wang M, Xu B, Wang H, Bu D, Wang J, Loor JJ. Effects of arginine concentration on the in vitro expression of casein and mTOR pathway related genes in mammary epithelial cells from dairy cattle. PLoS One 2014;9:e95985. https://doi.org/10.1371/journal.pone.0095985
  36. Wu S, Liu X, Cheng L, et al. Protective mechanism of leucine and isoleucine against H2O2-induced oxidative damage in bovine mammary epithelial cells. Oxid Med Cell Longev 2022;2022:22. https://doi.org/10.1155/2022/4013575
  37. Lin X, Li S, Zou Y, Zhao FQ, Liu J, Liu H. Lysine stimulates protein synthesis by promoting the expression of ATB0,+ and activating the mTOR pathway in bovine mammary epithelial cells. J Nutr 2018;148:1426-33. https://doi.org/10.1093/jn/nxy140
  38. Kim J, Lee JE, Lee JS, Park JS, Moon JO, Lee HG. Phenylalanine and valine differentially stimulate milk protein synthetic and energy-mediated pathway in immortalized bovine mammary epithelial cells. J Anim Sci Technol 2020;62:263-75. https://doi.org/10.5187/jast.2020.62.2.263
  39. Duan Y, Zeng L, Li F, et al. Effect of branched-chain amino acid ratio on the proliferation, differentiation, and expression levels of key regulators involved in protein metabolism of myocytes. Nutrition 2017;36:8-16. https://doi.org/10.1016/j.nut.2016.10.016
  40. Golias C, Charalabopoulos A, Charalabopoulos K. Cell proliferation and cell cycle control: a mini review. Int J Clin Pract 2004;58:1134-41. https://doi.org/10.1111/j.1742-1241.2004.00284.x
  41. Strzalka W, Ziemienowicz A. Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and cell cycle regulation. Ann Bot 2011;107:1127-40. https://doi.org/10.1093/aob/mcq243
  42. Wang Z. Regulation of cell cycle progression by growth factor-induced cell signaling. Cells 2021;10:3327. https://doi.org/10.3390/cells10123327
  43. Li Y, Cao Y, Wang J, et al. Kp-10 promotes bovine mammary epithelial cell proliferation by activating GPR54 and its downstream signaling pathways. J Cell Physiol 2020;235:4481-93. https://doi.org/10.1002/jcp.29325
  44. Zhen Z, Zhang M, Yuan X, Li M. Transcription factor E2F4 is a positive regulator of milk biosynthesis and proliferation of bovine mammary epithelial cells. Cell Biol Int 2020;44:229-41. https://doi.org/10.1002/cbin.11225
  45. Nakajima K, Itoh F, Nakamura M, et al. Opposing effects of lactoferrin on the proliferation of fibroblasts and epithelial cells from bovine mammary gland. J Dairy Sci 2015;98:1069-77. https://doi.org/10.3168/jds.2014-8430
  46. Ajita J, Saravanan S, Selvamurugan N. Effect of size of bioactive glass nanoparticles on mesenchymal stem cell proliferation for dental and orthopedic applications. Mater Sci Eng C 2015;53:142-9. https://doi.org/10.1016/j.msec.2015.04.041