奶山羊乳腺物质代谢研究
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摘要
乳腺拥有将各种营养物质转化成乳成分的能力,因此乳腺上皮细胞被称为“生物工厂”。泌乳是乳腺的主要功能,当哺乳动物独有的泌乳能力被激活时,乳腺向新生代提供成长和发育所需要的营养均衡的食品。乳腺泌乳功能与乳腺发育密切相关,乳腺发育主要在成年完成,由激素和生长因子进行调控。
乳腺的物质代谢是乳腺发育和成功泌乳的关键。本实验对乳腺的糖、脂和蛋白质代谢进行了系统研究。采用荧光定量RT-PCR方法研究了AKT1、PRLR、GLUT1、GLUT4、GLUT12、HKⅠ、HKⅡ、LALBA、β-1,4-半乳糖基转移酶mRNA在乳腺发育和泌乳各时期的表达,并使用免疫荧光组织化学和蛋白印记分析方法检测GLUT4在乳腺中的定位及其蛋白质水平的表达。使用HPLC方法测定乳腺和乳中的乳糖,以确定乳糖开始合成的时间及产量。结果显示AKT1、PRLR、GLUT1、GLUT12、HKⅠ、HKⅡ、LALBA、β-1,4-半乳糖基转移酶mRNA在泌乳期表达上调,GLUT4 mRNA在泌乳期下调。奶山羊乳腺基本糖代谢和乳糖合成均受PRLR、AKT1调控;奶山羊乳腺的主要葡萄糖转运蛋白是GLUT1,GLUT4和GLUT12也有表达;LALBA对于乳糖分泌的启动和维持至关重要;乳腺中乳糖最早出现在P150d。
选择与乳腺脂肪酸摄入(VLDLR、LPL、CD36)、外源胆固醇运输(ABCA1、ABCG2)、细胞内脂肪酸运输(FABP3、FABP4、ACBP)、脂肪酸长链(ACSL1)和短链(ACSS2、ACSS1)的激活、从头合成脂肪酸(ACACA、FAS)、去饱和(SCD、FADS1、FADS2)、三酰基甘油合成(AGPAT6、GPAM、LPIN、DGAT1、DGAT2)、脂质小滴形成(BTN1A1、XDH、ADFP、PLIN)、酮体利用(BDH1、OXCT1)和转录调节(INSIG1、INSIG2、SACP、PPARG、PPARGC1A、PPARGC1B、THRSP、SREBF1、SREBF2)、鞘磷脂合成(SPTLC2、LASS2、SGPL1、UGCG、OSBP、OSBP10)等相关的多个基因以及HSL、MLXIPL通过RT-PCR方法加以检测,结果显示大部分乳腺上皮细胞表达的基因在妊娠期和泌乳期上调,而脂肪细胞表达的基因则由于发育过程中脂肪的让位而下调。PRLR、AKT1对奶山羊乳腺脂代谢的调控主要是通过PRLR、AKT1对SREBP1的调控来实现。SREBP1、SREBP2和PPARG位于脂代谢调控网络的中心,山羊乳脂肪酸中C16:0、C18:1n9c和C18:1n9t含量最高。
研究4种酪蛋白(αs1-casein,αs2-casein,β-casein,κ-casein)与4种乳清蛋白(LGB, LALBA, LTF, WAP)mRNA在不同时期的表达,结果显示所有蛋白质mRNA都在泌乳期表达上调,其中LTF从P150d到L1d表达快速增加。同时检测与乳蛋白质转录和翻译作用相关的PRLR、AKT1、STAT5、ELF5、EIF4E-BP1、S6Kinase、Caveolin1 mRNA在乳腺中的表达,结果显示除EIF4E-BP1和Caveolin1外,其他基因的表达趋势与乳蛋白基本一致,提示其在乳蛋白转录或翻译过程中具有作用,而EIF4E-BP1、Caveolin1 mRNA的下调提示其具有泌乳抑制作用。编码奶山羊乳蛋白质基因的表达均在泌乳期升高,其中LTF在L1d达到峰值,提示其在泌乳启动中的重要作用。PRLR对奶山羊乳蛋白质合成转录水平的调控主要通过JAK2激活STAT5发挥作用,AKT1则通过mTOR对EIF4E-BP1的负调控和对S6激酶的正调控在翻译水平发挥作用。乳腺中β-酪蛋白最早出现在P90d。
Mammary gland has the ability to change nutrients into milk composition. Mammary gland epithelial cells is called as a“biological factory”for this. Lactation is the major function of mammry gland. Mammalian has exclusive function of lactation, when the ability is activated mammalian could provide food nutrition equilibrium for growth and development to neonatal progenies in different strains. This function relates to the special development of mamary galnd. Development of mammary gland completed almost in adulthood. It is regulated by hormones and growth factors complicated.
Substance metabolism of mammary gland is essential for its development and lactation. In this research, three aspects which included precursors in serum, key enzymes and transfer proteins in mammary gland and products in milk were chose to research the sustance metabolism of carbohydrates, lipids and proteins systematically. The research was devoted to study the changes of substance metabolism in process of mammary gland development and lactation especially. The relationships of these changes were also noticed.
Mammary gland can not synthesis glucose by itself, it can uptake glucose from serum by special transfer proteins to supply the energy and substance consumption in lactation. To research glucose metabolism fluorescent quantitative RT-PCR was used to study the mRNA expression of AKT1, PRLR, HKⅠ, HKⅡ, GLUT1, GLUT4, GLUT12, LALBA andβ-1, 4-galactosyl transferase in different development and lactation phases of mammary gland.
Immunofluorescence histochemistry and Western blotting analysis were used to study the location of GLUT4 and its expression of protein level in mammary gland respectively. HPLC was chose to detect the lactose in mamary gland and milk to determine the time point of lactose synthesis and its production. Results showed that the expressions of AKT1, PRLR, HKⅠ, HKⅡ, GLUT1, GLUT12, LALBA andβ-1, 4-galactosyl transferase mRNA up-regulated in lactation period, the expression of GLUT4 down-regulated in lactation period. Lactose appeared at P150d in mammary gland. To research the lipid metabolism in mammary gland some genes were chose from different aspects in lipid metabolism to detect their mRNA levels by fluorescent quantitative RT-PCR. They included: VLDLR, LPL, CD36 which related to the uptake of fatty acid. ABCA1, ABCG2 which related to the transport of foreign cholesterol. FABP3, FABP4, ACBP which related to the transport of fatty acid in cell. Activation of ACSL1, ACSS2, ACSS1. ACACA, FAS which related to the fatty acid de novo synthesis. SCD, FADS1, FADS2 which related to desaturation. AGPAT6, GPAM, LPIN, DGAT1, DGAT2 which related to the synthesis of triacylglycerol. BTN1A1, XDH, ADFP, PLIN which related to the formation of lipid droplets. BDH1 and OXCT1 which related to the using of ketone body. INSIG1, INSIG2, SCAP, PPARG, PPARGC1A, PPARGC1B, THRSP, SREBF1 and SREBF2 which related to transcriptional regulation. SPTLC2, LASS2, SGPL1, UGCG, OSBP and OSBP10 which related to the synthesis of sphingolipid. Results showed that most of genes expressed in mammary gland epithelium appeared up-regulated in pregnancy and lactation period. Some genes expressed in adipocytes appeared down-regulated in development may because of fatty resignation. According the results of genes detected a draft of metaboliam network for fat synthesis in dairy goat mammary gland was finished. C16:0, C18:1n9c and C18:1n9t contents were higher than the other fatty acids in goat milk.
In the research of protein metabolism, genes of four caseins and four whey proteins in different developmental periods were detected. The results showed all genes up-regulated in lactation period. The expression of lactoferrin mRNA increased dramatically in early lactation.The expression of PRLR, AKT1, STAT5, ELF5, EIF4BP1、S6Kinase and Caveolin1 mRNA which may related to protein metabolism in mammary gland were detected, the results showed that expect CAV1 and EIF4E-BP1 other genes had the same expression tendency with milk proteins. It implied that they involved in processes of transcription or translation of milk proteins. Down-regulation of CAV1 and EIF4E-BP1 demonstrated their negative roles in mammary gland. Genes of milk proteins were all up-regulated in lactation. The level of lactoferrin mRNA got peak value in L1d. The result implyed that lactoferrin gene plays an important role in secretory activation. PRLR regulates the transcription of milk proteins by the activation of STAT5 from JAK2. AKT1 regulates the translation of milk proteins by the regulation of mTOR to EIF4E-BP1 and S6K.β-casein was first appeared at P90d in goat mammary gland.
乳腺的物质代谢是乳腺发育和成功泌乳的关键。本实验对乳腺的糖、脂和蛋白质代谢进行了系统研究。采用荧光定量RT-PCR方法研究了AKT1、PRLR、GLUT1、GLUT4、GLUT12、HKⅠ、HKⅡ、LALBA、β-1,4-半乳糖基转移酶mRNA在乳腺发育和泌乳各时期的表达,并使用免疫荧光组织化学和蛋白印记分析方法检测GLUT4在乳腺中的定位及其蛋白质水平的表达。使用HPLC方法测定乳腺和乳中的乳糖,以确定乳糖开始合成的时间及产量。结果显示AKT1、PRLR、GLUT1、GLUT12、HKⅠ、HKⅡ、LALBA、β-1,4-半乳糖基转移酶mRNA在泌乳期表达上调,GLUT4 mRNA在泌乳期下调。奶山羊乳腺基本糖代谢和乳糖合成均受PRLR、AKT1调控;奶山羊乳腺的主要葡萄糖转运蛋白是GLUT1,GLUT4和GLUT12也有表达;LALBA对于乳糖分泌的启动和维持至关重要;乳腺中乳糖最早出现在P150d。
选择与乳腺脂肪酸摄入(VLDLR、LPL、CD36)、外源胆固醇运输(ABCA1、ABCG2)、细胞内脂肪酸运输(FABP3、FABP4、ACBP)、脂肪酸长链(ACSL1)和短链(ACSS2、ACSS1)的激活、从头合成脂肪酸(ACACA、FAS)、去饱和(SCD、FADS1、FADS2)、三酰基甘油合成(AGPAT6、GPAM、LPIN、DGAT1、DGAT2)、脂质小滴形成(BTN1A1、XDH、ADFP、PLIN)、酮体利用(BDH1、OXCT1)和转录调节(INSIG1、INSIG2、SACP、PPARG、PPARGC1A、PPARGC1B、THRSP、SREBF1、SREBF2)、鞘磷脂合成(SPTLC2、LASS2、SGPL1、UGCG、OSBP、OSBP10)等相关的多个基因以及HSL、MLXIPL通过RT-PCR方法加以检测,结果显示大部分乳腺上皮细胞表达的基因在妊娠期和泌乳期上调,而脂肪细胞表达的基因则由于发育过程中脂肪的让位而下调。PRLR、AKT1对奶山羊乳腺脂代谢的调控主要是通过PRLR、AKT1对SREBP1的调控来实现。SREBP1、SREBP2和PPARG位于脂代谢调控网络的中心,山羊乳脂肪酸中C16:0、C18:1n9c和C18:1n9t含量最高。
研究4种酪蛋白(αs1-casein,αs2-casein,β-casein,κ-casein)与4种乳清蛋白(LGB, LALBA, LTF, WAP)mRNA在不同时期的表达,结果显示所有蛋白质mRNA都在泌乳期表达上调,其中LTF从P150d到L1d表达快速增加。同时检测与乳蛋白质转录和翻译作用相关的PRLR、AKT1、STAT5、ELF5、EIF4E-BP1、S6Kinase、Caveolin1 mRNA在乳腺中的表达,结果显示除EIF4E-BP1和Caveolin1外,其他基因的表达趋势与乳蛋白基本一致,提示其在乳蛋白转录或翻译过程中具有作用,而EIF4E-BP1、Caveolin1 mRNA的下调提示其具有泌乳抑制作用。编码奶山羊乳蛋白质基因的表达均在泌乳期升高,其中LTF在L1d达到峰值,提示其在泌乳启动中的重要作用。PRLR对奶山羊乳蛋白质合成转录水平的调控主要通过JAK2激活STAT5发挥作用,AKT1则通过mTOR对EIF4E-BP1的负调控和对S6激酶的正调控在翻译水平发挥作用。乳腺中β-酪蛋白最早出现在P90d。
Mammary gland has the ability to change nutrients into milk composition. Mammary gland epithelial cells is called as a“biological factory”for this. Lactation is the major function of mammry gland. Mammalian has exclusive function of lactation, when the ability is activated mammalian could provide food nutrition equilibrium for growth and development to neonatal progenies in different strains. This function relates to the special development of mamary galnd. Development of mammary gland completed almost in adulthood. It is regulated by hormones and growth factors complicated.
Substance metabolism of mammary gland is essential for its development and lactation. In this research, three aspects which included precursors in serum, key enzymes and transfer proteins in mammary gland and products in milk were chose to research the sustance metabolism of carbohydrates, lipids and proteins systematically. The research was devoted to study the changes of substance metabolism in process of mammary gland development and lactation especially. The relationships of these changes were also noticed.
Mammary gland can not synthesis glucose by itself, it can uptake glucose from serum by special transfer proteins to supply the energy and substance consumption in lactation. To research glucose metabolism fluorescent quantitative RT-PCR was used to study the mRNA expression of AKT1, PRLR, HKⅠ, HKⅡ, GLUT1, GLUT4, GLUT12, LALBA andβ-1, 4-galactosyl transferase in different development and lactation phases of mammary gland.
Immunofluorescence histochemistry and Western blotting analysis were used to study the location of GLUT4 and its expression of protein level in mammary gland respectively. HPLC was chose to detect the lactose in mamary gland and milk to determine the time point of lactose synthesis and its production. Results showed that the expressions of AKT1, PRLR, HKⅠ, HKⅡ, GLUT1, GLUT12, LALBA andβ-1, 4-galactosyl transferase mRNA up-regulated in lactation period, the expression of GLUT4 down-regulated in lactation period. Lactose appeared at P150d in mammary gland. To research the lipid metabolism in mammary gland some genes were chose from different aspects in lipid metabolism to detect their mRNA levels by fluorescent quantitative RT-PCR. They included: VLDLR, LPL, CD36 which related to the uptake of fatty acid. ABCA1, ABCG2 which related to the transport of foreign cholesterol. FABP3, FABP4, ACBP which related to the transport of fatty acid in cell. Activation of ACSL1, ACSS2, ACSS1. ACACA, FAS which related to the fatty acid de novo synthesis. SCD, FADS1, FADS2 which related to desaturation. AGPAT6, GPAM, LPIN, DGAT1, DGAT2 which related to the synthesis of triacylglycerol. BTN1A1, XDH, ADFP, PLIN which related to the formation of lipid droplets. BDH1 and OXCT1 which related to the using of ketone body. INSIG1, INSIG2, SCAP, PPARG, PPARGC1A, PPARGC1B, THRSP, SREBF1 and SREBF2 which related to transcriptional regulation. SPTLC2, LASS2, SGPL1, UGCG, OSBP and OSBP10 which related to the synthesis of sphingolipid. Results showed that most of genes expressed in mammary gland epithelium appeared up-regulated in pregnancy and lactation period. Some genes expressed in adipocytes appeared down-regulated in development may because of fatty resignation. According the results of genes detected a draft of metaboliam network for fat synthesis in dairy goat mammary gland was finished. C16:0, C18:1n9c and C18:1n9t contents were higher than the other fatty acids in goat milk.
In the research of protein metabolism, genes of four caseins and four whey proteins in different developmental periods were detected. The results showed all genes up-regulated in lactation period. The expression of lactoferrin mRNA increased dramatically in early lactation.The expression of PRLR, AKT1, STAT5, ELF5, EIF4BP1、S6Kinase and Caveolin1 mRNA which may related to protein metabolism in mammary gland were detected, the results showed that expect CAV1 and EIF4E-BP1 other genes had the same expression tendency with milk proteins. It implied that they involved in processes of transcription or translation of milk proteins. Down-regulation of CAV1 and EIF4E-BP1 demonstrated their negative roles in mammary gland. Genes of milk proteins were all up-regulated in lactation. The level of lactoferrin mRNA got peak value in L1d. The result implyed that lactoferrin gene plays an important role in secretory activation. PRLR regulates the transcription of milk proteins by the activation of STAT5 from JAK2. AKT1 regulates the translation of milk proteins by the regulation of mTOR to EIF4E-BP1 and S6K.β-casein was first appeared at P90d in goat mammary gland.
引文
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Lucas BK, Ormandy CJ, Binart N, et al. Null mutation of the prolactin receptor gene produces a defect in maternal behavior. Endocrinology 1998, 139:4102-4107.
Magana MM, Lin SS, Dooley KA, Osborne TF. Sterol regulation of acetyl coenzyme A carboxylase promoter requires two interdependent binding sites for sterol regulatory element binding proteins. J Lipid Res 1997, 38:1630-1638.
Magana MM, Osborne TF. Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter. J Biol Chem 1996, 271:32689-32694.
McManaman JL, Palmer CA, Anderson S, Schwertfeger K, Neville MC. Regulation of milk lipid formation and secretion in the mouse mammary gland. Adv Exp Med Biol 2004, 554:263-279.
Memiya-Kudo M, Shimano H, Yoshikawa T, Yahagi N, Hasty AH, Okazaki H, Tamura Y, Shionoiri F, Iizuka Y, Ohashi K, et al. Promoter analysis of the mouse sterol regulatory elementbinding protein-1c gene. J Biol Chem 2000, 275:31078-31085.
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Mueckler M. Facilitative glucose transporters. Eur J Biochem 1994, 219:713-725.
Mulac-Jericevic B, Lydon JP, DeMayo FJ, et al. Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform. Proc Natl Acad Sci USA 2003, 100:9744-9749.
Naylor MJ, Ginsburg E, Iismaa TP, et al. The neuropeptide galanin augments lobuloalveolar development. J Biol Chem 2003, 278:29145-29152.
Naylor MJ, Oakes SR, Gardiner-Garden M, et al. Transcriptional changes underlying the secretory activation phase of mammary gland development. Mol Endocrinol 2005, 19:1868-1883.
Neville MC, McFadden TB, Forsyth I. Hormonal regulation of mammary differentiation and milk secretion. J Mammary Gland Biol Neoplasia 2002, 7:49-66.
Neville MC, Medina D, Monks J, et al. The mammary fat pad. J Mammary Gland Biol Neoplasia 1998, 3:109-116.
Nguyen D-A, Parlow AF, Neville MC. Hormonal regulation of tight junction closure in the mouse mammary epithelium during the transition from pregnancy to lactation. Endocrinology 2001,170:347-356.
Nielsen MO and K Jakobsen. Changes in mammary glucose and protein uptake in relation to milk synthesis during lactation in high- and low-yielding goats. Comp Biochem Physiol 1993, 106:359-365.
Oh SY, Park SK, Kim JW, Ahn YH, Park SW, Kim KS. Acetyl-CoA carboxylase b gene is regulated by sterol regulatory elementbinding protein-1 in liver. J Biol Chem 2003, 278:28410- 28417.
Ormandy CJ, Binart N, Kelly PA.: Mammary gland development in prolactin receptor knockout mice. J Mamm Gland Biol Neoplasi 1997, 2:355-364.
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Ormandy CJ, Naylor MJ, Harris J, Robertson F, Horseman ND, Lindeman GJ, Kelly PA. Investigation of the transcriptional changes underlying functional defects in the mammary glands of prolactin receptor knockout mice. Recent Prog Horm Res 2003, 58:297-323.
Palmer CA, Margaret C, Nevilli, et al. Analysis of lactation defects in transgenic mice. J Mammary Gland Biol Neoplasia 2006, 11:269-282.
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Porstmann T, Griffiths B, CHung Y-L, Delpuech O, Griffiths JR, Downward J, Schulze A. PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene 2005, 24:6465-6481.
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Samantha RO, Hiton HN, Ormandy CJ. The alveolar switch: coordinating the proliferative cues and cell fate decisions that drive the formation of lobuloalveoli from ductal epithelium. Breast Cancer Res 2006, 8:207
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Lucas BK, Ormandy CJ, Binart N, et al. Null mutation of the prolactin receptor gene produces a defect in maternal behavior. Endocrinology 1998, 139:4102-4107.
Magana MM, Lin SS, Dooley KA, Osborne TF. Sterol regulation of acetyl coenzyme A carboxylase promoter requires two interdependent binding sites for sterol regulatory element binding proteins. J Lipid Res 1997, 38:1630-1638.
Magana MM, Osborne TF. Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter. J Biol Chem 1996, 271:32689-32694.
McManaman JL, Palmer CA, Anderson S, Schwertfeger K, Neville MC. Regulation of milk lipid formation and secretion in the mouse mammary gland. Adv Exp Med Biol 2004, 554:263-279.
Memiya-Kudo M, Shimano H, Yoshikawa T, Yahagi N, Hasty AH, Okazaki H, Tamura Y, Shionoiri F, Iizuka Y, Ohashi K, et al. Promoter analysis of the mouse sterol regulatory elementbinding protein-1c gene. J Biol Chem 2000, 275:31078-31085.
Middleton RJ. Hexokinases and glucokinase. Biochem Soc Trans 1990, 18:4180-4183.
Mueckler M. Facilitative glucose transporters. Eur J Biochem 1994, 219:713-725.
Mulac-Jericevic B, Lydon JP, DeMayo FJ, et al. Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform. Proc Natl Acad Sci USA 2003, 100:9744-9749.
Naylor MJ, Ginsburg E, Iismaa TP, et al. The neuropeptide galanin augments lobuloalveolar development. J Biol Chem 2003, 278:29145-29152.
Naylor MJ, Oakes SR, Gardiner-Garden M, et al. Transcriptional changes underlying the secretory activation phase of mammary gland development. Mol Endocrinol 2005, 19:1868-1883.
Neville MC, McFadden TB, Forsyth I. Hormonal regulation of mammary differentiation and milk secretion. J Mammary Gland Biol Neoplasia 2002, 7:49-66.
Neville MC, Medina D, Monks J, et al. The mammary fat pad. J Mammary Gland Biol Neoplasia 1998, 3:109-116.
Nguyen D-A, Parlow AF, Neville MC. Hormonal regulation of tight junction closure in the mouse mammary epithelium during the transition from pregnancy to lactation. Endocrinology 2001,170:347-356.
Nielsen MO and K Jakobsen. Changes in mammary glucose and protein uptake in relation to milk synthesis during lactation in high- and low-yielding goats. Comp Biochem Physiol 1993, 106:359-365.
Oh SY, Park SK, Kim JW, Ahn YH, Park SW, Kim KS. Acetyl-CoA carboxylase b gene is regulated by sterol regulatory elementbinding protein-1 in liver. J Biol Chem 2003, 278:28410- 28417.
Ormandy CJ, Binart N, Kelly PA.: Mammary gland development in prolactin receptor knockout mice. J Mamm Gland Biol Neoplasi 1997, 2:355-364.
Ormandy CJ, Camus A, Barra J, et al. Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev 1997, 11:167-178.
Ormandy CJ, Naylor MJ, Harris J, Robertson F, Horseman ND, Lindeman GJ, Kelly PA. Investigation of the transcriptional changes underlying functional defects in the mammary glands of prolactin receptor knockout mice. Recent Prog Horm Res 2003, 58:297-323.
Palmer CA, Margaret C, Nevilli, et al. Analysis of lactation defects in transgenic mice. J Mammary Gland Biol Neoplasia 2006, 11:269-282.
Pilla F, Valentini A, Lenstra JA et al. Animal genetics and functional foods; livestock forming systems; product quality based on local resources leading to improved sustainability. Wageningen Academic Publishers. EAAP Publications 2006, 118:49-59.
Porstmann T, Griffiths B, CHung Y-L, Delpuech O, Griffiths JR, Downward J, Schulze A. PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene 2005, 24:6465-6481.
Printz RL, H Osawa, H Ardehali, S Koch, and DK. Granner. HexokinaseⅡgene: structure, regulation and promoter organization. Biochem Soc Trans 1997, 25: 107-112.
Redpath NT, Foulstone EJ, Proud CG. Regulation of translocation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J 1996, 15:2291-2297.
Richert MM, Schwertfeger KL, Ryder JW, Anderson SM. An atlas of mouse mammary gland development. J Mammary Gland Biol Neoplasia 2000, 5:227-241.
Rosen JM, O’Neal DL, McHugh JE, Comstock JP. Progesterone-mediated inhibition of casein mRNA and polysomal casein synthesis in the rat mammary gland during pregnancy. Biochemistry 1978, 17:290-297.
Rudolph MC, Manaman JL, Hunter L, Phang T, et al. Functional development of the mammary gland: use of expression profiling and trajectory clustering to reveal changes in gene expression during pregnancy, lactation, and involution. J Mammary Gland Biol Neoplasia 2003, 8:287-307.
γRudolph MC, McManaman JL, Phang T, Russel T, Kominsky DM, Serkova N, et al. Metabolic regulation in the lactating mammary gland: A lipid synthesizing machine. Physiol Genomics 2007, 28:323-336.
Said TK, Conneely OM, Medina D, et al. Progesterone, in addition to estrogen, induces cyclin D1 expression in the murine mammary epithelial cell, in vivo. Endocrinology 1997, 138:3933-3939.
Samantha RO, Hiton HN, Ormandy CJ. The alveolar switch: coordinating the proliferative cues and cell fate decisions that drive the formation of lobuloalveoli from ductal epithelium. Breast Cancer Res 2006, 8:207
Sato R, Inoue J, Kawabe Y, Kodama T, Takano T, Maeda M. Sterol-dependent transcriptional regulation of sterol regulatory element-binding protein-2. J Biol Chem 1996, 271:26461-26464.
Schmitt-ney M, Doppler W, Ball RK, Groner B: b-casein gene promoter activity is regulated by the hormone mediated relief of transcriptional repression and a mammary-gland-specific nuclear factor. Mol Cell Biol 1991, 11:3745-3755.
Schweizer M, Roder K, Zhang L, Wolf SS. Transcription factors acting on the promoter of rat fatty acid synthase gene. Biochem Soc Trans 2002, 30:1070-1072.
Schwertfeger KL, McManaman JL, Palmer CA, Neville MC, Anderson SM. Expression ofconstitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation. J Lipid Res 2003, 44:1100-1112.
Shackleton MFV, Simpson KJ, et al. Generation of a functional mammary gland from a single stem cell. Nature 2006, 439:84-88.
Smalley M, Ashworth A. Stem cells and breast cancer: A field in transit. Nat Rev Cancer 2003, 3:832-844.
Smalley MJ, Clarke RB. The mammary gland“side population”: a putative stem/progenitor cell marker? J Mammary Gland Biol Neoplasia 2005, 10:37-47.
Smith GH, Boulanger CA. Mammary epithelial stem cells: transplantation and self-renewal analysis. Cell Prolif 2003, 36: 3-15.
Stein T, Morris J, Davies C, Weber-Hall S, Duffy MA, Heath V, Bell A, Ferrier R, Sandilands G, Gusterson B. Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3. Breast Cancer Res 2004, 6:R75-R91.
Stingl J, Raouf A, Emerman JT, et al. Epithelial progenitors in the normal human mammary gland. J Mammary Gland Biol Neoplasia 2005, 10:49-59.
Streuli CH, Edwards GM, Delcommenne M, et al. Stat5 as a target for regulation by extracellular matrix. J Biol Chem 1995, 270:21639-21644.
Traurig H. Cell Proliferation in the mammary gland during late pregnancy and lactation. Anatomical Record 1967, 157:489-503.
Travers MT, Vallance AJ, Gourlay HT, Gill CA, Klein I, Bottema CB, Barber MC. Promoter I of the ovine acetyl-CoA carboxy-lase-alpha-gene: An E-box motif at -114 in the proximal promoter binds upstream stimulatory factor (USF)-1 and USF-2 and acts as an insulin-response sequence in differentiating adipocytes. Biochem J 2001, 359:273-284.
Ureta T. The comparative isozymology of vertebrate hexokinases. Comp Biochem Physiol B 1982, 71:549-555.
Wilson JE. Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 2003, 206:2049-2057.
Wynick D, Hammond PJ, Akinsanya KO, et al. Galanin regulates basal and oestrogen-stimulated lactotroph function. Nature 1993, 364:529-532.
Wynick D, Small CJ, Bacon A, et al. Galanin regulates prolactin release and lactotroph proliferation. Proc Natl Acad Sci USA 1998, 95:12671-12676.
曲波.奶山羊乳腺发育的形态学研究[D].中国博士学位论文全文数据库,2008, (03)