激素对奶牛乳腺上皮细胞乳脂肪合成的调控作用

doi:10.16431/j.cnki.1671-7236.2021.08.011

摘要/Abstract

摘要： 乳脂肪是高质量的天然脂肪，其可为人类提供营养和能量，在各种膳食脂肪和油类中，是最容易被消化吸收的。乳脂肪是在乳腺中由从头合成或外源摄取的脂肪酸与甘油酯化形成的一种脂类物质，其含量的高低关系着牛奶品质的优劣和乳制品的加工特性。在奶牛的泌乳周期中，乳腺泌乳功能受多种因素影响，其中内分泌腺分泌的多种激素对奶牛乳腺上皮细胞（BMECs）乳脂的合成具有积极的调控作用。综上所述，作者介绍了氢化可的松、催乳素、胰岛素和生长激素4种泌乳相关激素对BMECs乳脂肪合成的调控机理，即从乳脂合成适宜的激素添加量、激素对乳脂球形态的影响方面初步阐释其调控作用，并从乳脂合成的关键酶及转录因子、激素对乳脂合成相关基因表达量方面深入阐释其作用机理，旨在为研究泌乳相关激素对奶牛乳腺内乳脂肪合成的调控机理提供参考。

关键词: 奶牛乳腺上皮细胞; 乳脂肪; 氢化可的松; 催乳素; 胰岛素; 生长激素

Abstract: Milk fat is a high quality natural fat which can provide nutrition and energy for human.Among all kinds of dietary fat and oil, it is the easiest to be digested and absorbed.Milk fat is a kind of lipid substance formed by esterification of de novo synthesis or exogenous intake of fatty acid and glycerol in the mammary gland, its content is related to the quality of milk and the processing characteristics of dairy products.During the lactation cycle of dairy cows, the lactation function of mammary gland is affected by many factors, among which a variety of hormones secreted by the endocrine glands have positive regulatory effects on the synthesis of milk fat in bovine mammary epithelial cells.To sum up, the authors introduced the regulatory mechanism of hydrocortisone, prolactin, insulin and growth hormone on milk fat synthesis in bovine mammary epithelial cells, explaining its regulatory effect from the appropriate amount of hormone in milk fat synthesis and the effect of hormone on the morphology of milk fat globule.And from the key enzymes of milk fat synthesis and transcription factors, hormones on the expression of milk fat synthesis-related genes, the mechanism is explained in depth, aiming to provide reference for studying the regulation mechanism of lactation-related hormones on milk fat synthesis in dairy cows' mammary glands.

Key words: bovine mammary epithelial cells; milk fat; hydrocortisone; prolactin; insulin; growth hormone

中图分类号:

S823.9⁺1

曹越, 李大彪. 激素对奶牛乳腺上皮细胞乳脂肪合成的调控作用[J]. 中国畜牧兽医, 2021, 48(8): 2778-2786.

CAO Yue, LI Dabiao. Regulatory Effects of Hormones on Milk Fat Synthesis in Bovine Mammary Epithelial Cells[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(8): 2778-2786.

参考文献

[1] FEUERMANN Y,MABJEESH S J,SHAMAY A.Mammary fat can adjust prolactin effect on mammary epithelial cells via leptin and estrogen[J].International Journal of Endocrinology,2009,2009:427260.
[2] FUSCH G,MITRA S,ROCHOW N,et al.Target fortification of breast milk:Levels of fat,protein or lactose are not related[J].Acta Paediatrica,2015,104(1):38-42.
[3] 孙梅.激素和细胞因子对奶牛乳腺上皮细胞乳蛋白和乳脂肪合成的影响[D].呼和浩特:内蒙古农业大学,2018. SUN M.Effects of hormone and cytokines on milk protein and milk fat synthesis in bovine mammary epithelial cells[D].Hohhot:Inner Mongolia Agricultural University,2018.(in Chinese)
[4] MA L.Regulatory factors of milk fat synthesis in dairy cows[D].Virginia:Virginia Polytechnic Institute and State University,2012.
[5] ZIDI A,SERRADILLA J M,JORDANA J,et al.Pleiotropic effects of the goat prolactin receptor genotype on milk fatty acid composition[J].Domestic Animal Endocrinolog,2010,39(2):85-95.
[6] 吕威.原代奶牛乳腺上皮细胞的分离、培养和传代的技术研究[D].哈尔滨:东北农业大学,2016. LYU W.Primary bovine epithelial cells were isolated,culture and passaged technology[D].Harbin:Northeast Agricultural University,2016.(in Chinese)
[7] 孟丽丽,钟凯,朱河水.乳腺上皮细胞在乳腺炎症反应中的作用[J].中国畜牧兽医,2009,36(12):103-105. MENG L L,ZHONG K,ZHU H S.Actions of mammary epithelial cells in mastitis[J].China Animal Husbandry & Veterinary Medicine,2009,36(12):103-105.(in Chinese)
[8] SORG D,FANDREY E,FRLICH K,et al.Mammary immunity of White Park and Highland cattle compared with Brown Swiss and Red Holstein[J].Animal Genetic Resources,2013,52:91-104.
[9] 崔立莉.奶牛乳腺上皮细胞体外培养体系的建立及其应用[D].乌鲁木齐:新疆农业大学,2006. CUI L L.Establishment and application of in vitro culture system of bovine mammary epithelial cells[D].Urumqi:Xinjiang Agricultural University,2006.(in Chinese)
[10] CRAVERO D,MARTIGNANI E,MIRETTI S,et al.Bovine mammary epithelial cells retain stem-like phenotype in longterm cultures[J].Research in Veterinary Science,2015,97(2):367-375.
[11] BIONAZ M,LOOR J J.Gene networks driving bovine mammary protein synthesis during the lactation cycle[J].Bioinformatics and Biology Insights,2011,5:83-98.
[12] WANG G Q,BONKOVSKY H L,DELEMOS A D,et al.Recent insights into the biological functions of liver fatty acid binding protein 1[J].Journal of Lipid Research,2015,56(12):2238-2247.
[13] MARTIN C,CHEVROT M,POIRIER H,et al.CD36 as a lipid sensor[J].Physiological Behavior,2011,105(1):36-42.
[14] PEPINO M Y,KUDA O,SAMOVSKI D,et al.Structure function of CD36 and importance of fatty acid signal transduction in fat metabolism[J].Annual Review Nutrition,2014,34(1):281-303.
[15] 邢媛媛.二、三维培养模式下添加激素对奶牛乳腺上皮细胞乳脂肪和乳蛋白合成的影响[D].呼和浩特:内蒙古农业大学,2017. XING Y Y.Effect of hormone supplementation on milk fat and milk protein synthesis in two and three-dimensional cultured bovine mammary epithelial cells[D].Hohhot:Inner Mongolia Agricultural University,2017.(in Chinese)
[16] BIONAZ M,LOOR J J.ACSL1,AGPAT6,FABP3,LPIN1 and SLC27A6 are the most abundant isoformsin bovine mammary tissue and their expression is affected by stage of lactation[J].Journal of Nutrition,2008,138(6):1019-1024.
[17] SMITH V G,EDGERTON L A,HAFS H D,et al.Bovine serumestrogens,progestins and glucocorticoids during late pregnancy,parturition and early lactation[J].Journal of Animal Science,1973,36(2):391-396.
[18] HILLGARTNER F B,SALATI L M,GOODRIDGE A G.Physiological and molecular mechanisms involved in nutritional regulation of fatty acid synthesis[J].Physiological Reviews,1995,75(1):47-76.
[19] KIM T S,FREAKE H C.High carbohydrate diet and starvation regulate lipogenic mRNA in rats in a tissue specific manner[J].Journal of Animal Nutrition,1996,126(3):611-617.
[20] 胡菡,王加启,李发弟,等.奶牛乳腺脂肪酸合成相关基因研究进展[J].生物技术通报,2009,10:34-39. HU H,WANG J Q,LI F D,et al.Advance of fatty acid synthesis regulated genes from dairy cow[J].Biotechnology Bulletin,2009,10:34-39.(in Chinese)
[21] BESWICK N S,KENNELLY J J.The influence of bovine growth hormone and growth hormone releasing factor on acetyl-CoA carboxylase and fatty acid synthase in primiparous Holstein cows[J].Comparative Biochemistry and Physiology C:Pharmacology,Toxicology and Endocrinology,1998,120(2):241-249.
[22] ABU-EIHEIGA L,BRINKLEY W R,ZHONG L.The subcellular localization of acetyl-CoA carboxylase 2[J].Proceedings of the National Academy of Sciences of the United States of America,2000,97(4):1444-1449.
[23] FOX P F,MCSWEENEY P L H.Advanced dairy chemistry volume 2 lipids volume 18Ⅱ Composition and structure of bovine milk lipids[J].On Academic,2006,9(1):1-42.
[24] HORTON J D,GOLDSTENIN J L,BROWN M S.SREBPs:Activators of the complete program of cholesterol and fatty acid synthesis in the liver[J].Journal of Clinical Investigation,2002,109(9):1125-1131.
[25] 王加启.牛奶乳脂肪和乳蛋白的合成与调控机理[J].饲料与畜牧,2011,2:8-14. WANG J Q.Synthesis and regulatory mechanism of milk fat and milk protein[J].Animal Agriculture,2011,2:8-14.(in Chinese)
[26] LI N,ZHAO F,WEI C J,et al.Function of SREBP1 in the milk fat synthesis of dairy cow mammary epithelial cells[J].International Journal of Molecular Sciences,2014,15(9):16998-17013.
[27] MA L,CORL B A.Transcriptional regulation of lipid synthesis in bovine mammary epithelial cells by sterol regulatory element binding protein-1[J].Journal of Dairy Science,2012,95(7):3743-3755.
[28] LOLLIVIER V,LACASSE P,ARIZALA J A,et al.In vivo inhibition followed by exogenous supplementation demonstrates galactopoietic effects of prolactin on mammary tissue and milk production in dairy cows[J].Journal of Dairy Science,2015,98(12):8775-8787.
[29] 王红芳,杨维仁,刘建新,等.固醇调控元件结合蛋白及其对乳脂合成的调节作用[J].动物营养学报,2010,22(5):1165-1170. WANG H F,YANG W R,LIU J X,et al.Sterol regulatory element-binding proteins(SREBPs) and their roles in synthesis of milk fat[J].Chinese Journal of Animal Nutrition,2010,22(5):1165-1170.(in Chinese)
[30] BRAISSANT O,FOUFELLE F,SCOTTO C,et al.Differential expression of peroxisome profilerator activated receptors(PPARs):Tissue distribution of PPAR-alpha,-beta,and -gamma in the adult rat[J].Endocrinology,1996,137(1):354-366.
[31] KANG Y,HENGBO S,JUN L,et al.PPARG modulated lipid accumulation in dairy GMEC via regulation of ADRP gene[J].Journal of Cellular Biochemistry,2015,116(1):192-201.
[32] SARRAF P,MUELLER E,SMITH W M,et al.Loss of function mutations in PPAR gamma associated with human colon cancer[J].Molecular Cell,1999,3(6):799-804.
[33] KAWAIAND M,ROSEN C J,KAWAIAND M,et al.PPARγ:A circadian transcription factor in adipogenesis and osteogenesis[J].Nature Reviews Endocrinology,2010,6(11):629-636.
[34] LEE S H,HOSSNER K L,Coordinate regulation of ovine adipose tissue gene expression by propionate[J].Journal of Animal Science,2002,80(11):2840-2849.
[35] BIONAZ M,CHEN S,KHAN M J,et al.Functional role of PPARs in ruminants:Potential targets for fine-tuning metabolism during growth and lactation[J].PPAR Research,2013,4(29):138-145.
[36] KADEGOWDA A K,BIONAZ M,PIPEROVA L S,et al.Peroxisome proliferator activated receptor gamma activation and long-chain fatty acids alter lipogenic gene networks in bovine mammary epithelial cells to various extents[J].Journal of Dairy Science,2009,92(9):4276-4289.
[37] WANG C,LIU J X,YUAN Z P,et al.Effect of level of metabolizable protein on milk production and nitrogen utilization in lactating dairy cows[J].Journal of Dairy Science,2007,90(6):2960-2965.
[38] 魏宏阳,王加启.添加游离不饱和脂肪酸或植物油对瘤胃微生物体外发酵及微晶纤维素降解的影响[J].畜牧兽医学报,2004,35(5):491-497. WEI H Y,WANG J Q.Effects of free unsaturated fatty acid mixture and vegetable oils on pure cellulose degradation and fermentation by mixed ruminal microbes in vitro[J].Acta Veterinaria et Zootechnica Sinica,2004,35(5):491-497.(in Chinese)
[39] SHAO Y,WALL E H,MCFADDEN T B,et al.Effects of free unsaturated fatty acid mixture and vegetable oils on pure cellulose degradation and fermentation by mixed ruminal microbes in vitro[J].Domestic Animal Endocrinology,2013,44(2):57-69.
[40] TUCKER H A.Symposium:Hormonal regulation of milk synthesis hormones,mammary growth and lactation:A 41 year perspective[J].Journal of Dairy Science,2000,83(4):874-884.
[41] COLLIER R J,BAUMAN D E,HAYS R L.Lactogenesis in explant cultures of mammary tissue from pregnant cows[J].Endocrinology,1977,100(4):1192-1200.
[42] 田青,王洪荣,王梦芝.氢化可的松对奶牛乳腺上皮细胞酪蛋白合成的影响[J].畜牧兽医学报,2014,45(10):1663-1670. TIAN Q,WANG H R,WANG M Z.Effects of HYD on the synthesis of casein in mammary epithelial cells of Holstein cows in vitro[J].Acta Veterinaria et Zootechnica Sinica,2014,45(10):1663-1670.(in Chinese)
[43] SILVA L G,FERGUSON B S,FACIOLA A P.Rapid communication:Prolactin and hydrocortisone impact TNF-α mediated mitogen activated protein kinase signaling and inflammation of bovine mammary epithelial (MAC-T) cells[J].Journal of Animal Science,2017,95(12):5524-5531.
[44] 殷立恒.PRL、GC对奶牛脂肪细胞和肝细胞脂代谢的影响[D].长春:吉林大学,2015. YIN L H.Effects of PRL and GC on lipid metabolism in adipocytes and hepatocytes of dairy cows[D].Changchun:Jilin University,2015.(in Chinese)
[45] 孙晓静.奶牛泌乳相关激素周期性变化规律及激素对乳腺外植体中基因表达的影响[D].泰安:山东农业大学,2012. SUN X J.Periodic change of bovine lactation-related hormones and the effect of hormones on gene expression in bovine mammary gland explants[D].Tai'an:Shandong Agricultural University,2012.(in Chinese)
[46] 孙梅.氢化可的松对奶牛乳腺上皮细胞乳脂肪合成的影响[J].中国细胞生物学学报,2017,39(9):1156-1164. SUN M.The effect of hydrocortisone on milk fat synthesis in bovine mammary epithelial cells[J].Chinese Journal of Cell Biology,2017,39(9):1156-1164.(in Chinese)
[47] WU W,CHEN Y H,UEDA E,et al.Different forms of prolactin have opposing effects on the expression of cellcycle regulatory proteins in differentiated mammary epithelial cells[J].Oncology Research,2006,16(2):75-84.
[48] FLINT D J,KNIGHT C H.Interactions of prolactin and growth hormone (GH) in the regulation of mammary gland function and epithelial cell survival[J].Journal of Mammary Gland Biology and Neoplasia,1997,2(1):41-48.
[49] WALL E H,CRAWFORD H M,ELLIS S E,et al.Mammary response to exogenous prolactin or frequent milking during early lactation in dairy cows[J].Journal of Dairy Science,2006,89(12):4640-4648.
[50] 田青,王洪荣.胰岛素、催乳素和氢化可的松对奶牛乳腺上皮细胞增殖和凋亡的影响[J].中国饲料,2013,2:8-12. TIAN Q,WANG H R.Effects of INS,PRL and HYD on proliferation and apoptosis of mammary epithelial cells of dairy cows in vitro[J].China Feed,2013,2:8-12.(in Chinese)
[51] HOUDEBINE L M,TEYSSOT B,DJIANE J,et al.Control of the expression of milk protein genes by prolactin,glucocorticoids and progesterone[J].Annales D'Endocrinologie,1982,43(5):354-369.
[52] KABOTYANSKI E B,RIJNKELS M,FREEMAN-ZADROW C,et al.Lactogenic hormonal induction of long distance interactions between beta-casein gene regulatory elements[J].The Journal of Biological Chemistry,2009,284(34):22815-22824.
[53] CHUNG E R,RHIM T J,HAN S K.Associations between PCR-RFLP markers of growth hormone and prolactin genes and production traits in dairy carrel[J].Journal of Dairy Science,1996,38:321-336.
[54] BEN-JONATHAN N,HUGO E R,BRANDEBOURGT D,et al.Focus on prolactin as a metabolic hormone[J].Trends in Endocrinology and Metabolism,2006,17(3):110-116.
[55] 王春艳.瘦素对奶牛乳腺上皮细胞乳蛋白合成的调控作用研究[D].呼和浩特:内蒙古农业大学,2012. WANG C Y.Effects of leptin on milk protein synthesis in bovine mammary epithelial cells[D].Hohhot:Inner Mongolia Agricultural University,2012.(in Chinese)
[56] AKERS R M.Major advances associated with hormone and growth factor regulation of mammary growth and lactation in dairy cows[J].Journal of Dairy Science,2006,89(4):1222-1234.
[57] 邢媛媛.催乳素对奶牛乳腺上皮细胞乳脂和乳蛋白合成相关基因表达的影响[J].动物营养学报,2016,28(8):2439-2447. XING Y Y.Effects of prolactin on gene expressions invlved in milk fat and milk protein synthesis in bovine mammary epithelial cells[J].Chinese Journal of Animal Nutrition,2016,28(8):2439-2447.(in Chinese)
[58] 李真,李庆章.奶山羊乳腺发育过程中生长激素、胰岛素及其受体的变化规律研究[J].中国农业科学,2010,43(8):1730-1737. LI Z,LI Q Z.Development change of growth hormone,insulin and their receptors in mammary gland of dairy goats[J].Scientia Agricultura Sinica,2010,43(8):1730-1737.(in Chinese)
[59] MENZIES K K,LEFEVRE C,MACMILLAN K L,et al.Insulin regulates milk protein synthesis at multiple levels in the bovine mammary gland[J].Functional Integrative Genomics,2009,9(2):197-217.
[60] GUO Z X,CHENG X O,FENG K Y,et al.The mTORC1/4EBP1/PPARγ axis mediates insulin-induced lipogenesis by regulating lipogenic gene expression in bovine mammary epithelial cells[J].Journal of Agricultural and Food Chemistry,2019,67(21):6007-6018.
[61] PAUCIULLO A,COSENZA G,STERI R,et al.A single nucleotide polymorphism in the promoter region of river buffalo stearoyl CoA desaturase gene (SCD) is associated with milk yield[J].Journal of Dairy Research,2012,79(4):429-435.
[62] 林先滋,罗军,张犁苹,等.miR-200a对奶山羊乳腺上皮细胞乳脂合成相关基因mRNA表达的影响[J].畜牧兽医学报,2012,43(7):1028-1036. LIN X Z,LUO J,ZHANG L P,et al.The effect of miR-200a on gene mRNA expression related to milk fat synthesis in dairy goat mammary gland epithelial cells[J].Acta Veterinaria et Zootechnica Sinica,2012,43(7):1028-1036.(in Chinese)
[63] 王皓宇,秦彤,郝海生,等.胰岛素对体外培养奶牛乳腺上皮细胞乳蛋白、乳脂肪合成相关基因mRNA表达的影响[J].畜牧兽医学报,2013,5(8):710-718. WANG H Y,QIN T,HAO H S,et al.Effects of insulin on mRNA expression of genes related to milk protein and fat synthesis in bovine mammary epithelial cells cultured in vitro[J].Acta Veterinaria et Zootechnica Sinica,2013,5(8):710-718.(in Chinese)
[64] RABKIN R,SUN D F,CHEN Y,et al.Growth hormone resistance in uremia aroleforimpaired JAK/sunsignaling[J].Pediatric Nephorlogy,2005,20(3):313-318.
[65] BANMAN D E.Bovine somatorpin and laction:From basic science to commercial application[J].Domestic Animal Endocrinology,1999,17(2-3):101-116.
[66] NEVILLE M C,MEDINA D,MONKS J,et al.The mammary fat pad[J].Journal of Mammary Gland Biology & Neoplasia,1998,3(2):109-116.
[67] 季昀,庞学燕,田青,等.生长激素和胰岛素样生长因子Ⅰ对奶牛乳蛋白合成关键激酶及调节因子mRNA表达量的影响[J].动物营养学报,2013,25(1):198-207. JI Y,PANG X Y,TIAN Q,et al.Growth hormone and insulin-like growth factor Ⅰ:Effects on mRNA expression levels of key kinases and regulatory factors regulating milk protein synthesis[J].Chinese Journal of Animal Nutrition,2013,25(1):198-207.(in Chinese)
[68] VELEZ J C,DONKIN S S.Bovine somatotropin increses hepatic phosphoenol pyruvate carboxykinase mRNA in lactating dairy cows[J].Journal of Dairy Science,2004,87(5):1325-1335.
[69] WANG B,SHI L,MEN J,et al.Controlled synchronization of prolactin/STAT5 and AKT1/mTOR in bovine mammary epithelial cells[J].In Vitro Cellular & Developmental Biology,2020,56(3):243-252.
[70] WANG M Z,JI Y,WANG C,et al.The preliminary study on the effects of growth hormone and insulin-like growth factor-Ⅰon K-casein synthesis in bovine mammary epithelial cells in vitro[J].Journal of Animal Physiology and Animal Nutrition,2016,100(2):251-255.
[71] BARBANO D M,LYNCH J M,BAUMAN D E,et al.Effect of prolonged release formulation of N-methionyl bovine somatotropin on milk fat[J].Journal of Dairy Science,1992,75(7):1775-1793.
[72] DANT P D,LANNA,HOUSEKNECHT K L,et al.Effect of somatotropin treatment on lipogenesis,lipolysis and related cellular mechanisms in adipose tissue of lactating cows[J].Journal of Dairy Science,1995,78(8):1703-1712.