乳脂肪和乳蛋白主要前体物对DCAPCs中GH和PRL的影响及机制研究
|
摘要
牛奶营养品质低下已成为我国奶业健康发展所面临的严峻挑战之一。乳脂肪和乳蛋白是决定牛奶营养品质的主要物质。牛奶营养品质受多种因素影响，其中神经内分泌因素对乳脂肪和乳蛋白含量具有重要的调控作用。生长激素（growthhormone, GH）和催乳素（prolactin, PRL）可以调控奶牛乳脂肪和乳蛋白前体物的生成、摄取和利用。而乳脂肪和乳蛋白前体物也可以通过直接或间接作用调控牛垂体组织泌乳相关激素的合成和分泌。为深入认识乳脂肪和乳蛋白前体物对奶牛GH和PRL合成和分泌的影响及机制，本研究建立了体外培养奶牛腺垂体细胞（dairy cow anterior pituitary cells, DCAPCs）的方法，研究了短链脂肪酸（short-chain fatty acids, SCFAs）、β-羟丁酸（β-hydroxybutyric acid, BHBA）、精氨酸和酪氨酸对DCAPCs中GH和PRL合成和分泌的影响及其分子机制，初步构建了调控乳脂肪和乳蛋白合成的营养与激素相互作用网络，以期为全面认知乳脂肪和乳蛋白合成关键物质代谢的神经内分泌调节机制提供参考。
免疫组织化学法研究发现奶牛腺垂体组织中生长激素分泌细胞主要位于腺垂体侧翼区下缘，而催乳素分泌细胞主要位于腺垂体侧翼区上缘。取腺垂体侧翼区组织块，用含有0.3%I型胶原酶、0.1%透明质酸酶、0.01%DNA酶的无钙镁离子Hanks液消化3h后，获得的垂体细胞接种培养5d后可见形状规则的铺路石样上皮细胞，经免疫组织化学法鉴定可分泌GH和PRL，可以用于进一步试验。
SCFAs可以与DCAPCs中的GPR41/43结合，活化抑制型G蛋白α亚基（inhibitory G protein alpha subunit, Gαi），抑制细胞内腺苷酸环化酶（adenylylcyclase, AC）活性，降低胞内cAMP含量，导致细胞内蛋白激酶A（protein kinaseA, PKA）活性降低，进而降低cAMP反应元件结合蛋白（cAMP response elementbinding protein, CREB）磷酸化水平，最终抑制GH基因转录。而磷酸化的CREB可能通过调节细胞内垂体特异性转录因子-1（pituitary-specific transcription factor-1, Pit-1）活性间接抑制GH和PRL基因转录。100ng/L剂量的百日咳毒素（pertussis toxin, PTX）预处理DCAPCs2h可部分逆转SCFAs的上述作用，证实SCFAs可以通过cAMP/PKA/CREB通路调节牛GH和PRL基因表达。此外，SCFAs可降低DCAPCs的细胞活性，这也是导致GH和PRL分泌量减少的原因之一。
BHBA可以通过与DCAPCs细胞膜上的GPR109A相结合，激活Gαi蛋白，抑制AC的酶活性，下调胞内cAMP含量，降低PKA活性和CREB磷酸化水平，最终抑制GH的转录，并通过抑制Pit-1的合成来间接降低GH和PRL表达。此外，BHBA可以刺激MCT1的表达，活化低糖或无糖培养的DCAPCs中AMPK分子，并可能通过抑制mTOR功能减少GH和PRL mRNA的翻译，导致GH和PRL分泌量减少。
精氨酸可在一氧化氮合成酶（nitric oxide synthase, NOS）的催化作用下生成NO，促进细胞外Ca2+内流，进而调节DCAPCs中GH和PRL的合成与分泌，且50-75mg/L的精氨酸促进GH、PRL合成与分泌效果最佳。酪氨酸可在酪氨酸羟化酶（tyrosine hydroxylase, TH）催化作用下代谢为多巴胺，并以自分泌或旁分泌的方式抑制DCAPCs中PRL合成和分泌。
此外，本研究还借鉴相关研究资料和方法，初步构建了调控乳脂肪和乳蛋白合成的营养与激素相互作用网络，以期为深入研究乳脂肪和乳蛋白合成调控机制和改善牛奶营养品质提供科学依据。
Low nutritional quality of cow’s milk has increasingly become a severechallenge faced by the healthy development of dairy industry in China. Milk fat andprotein are the main substances to determine the nutritional quality of cow’s milk.Cow’s milk quality could be affected by many factors, where neuroendocrine factorsplay an important regulatory role to fat and protein contents in cow’s milk. Growthhormone (GH) and prolactin (PRL) is the most important hormone for the regulationof milk protein and milk fat synthesis in dairy cows. The concentration of precursorsof milk components in serum may also regulate the GH and PRL synthesis orsecretion in dairy cow anterior pituitary cells (DCAPCs) with direct or indirectmanners. Therefore, the objective of the present experiment was to investigate theeffects and signaling mechanisms of short-chain fatty acids (SCFAs), β-hydroxy-butyric acid (BHBA), arginin, and tyrosine on the GH and PRL synthesis or secretionin DCAPCs cultured in vitro. In addition, the nutrient-hormone interaction networksregulating milk fat and milk protein synthesis were constructed to get a thoroughunderstanding about the effects and molecular mechanisms of neuroendocrine factorson fatty acid and protein synthesis of cow’s milk.
Immunohistochemistry assay of GH in the anterior pituitary glands showed thatmost somatotrophs were located within the lateral wings inferior border of the anteriorpituitary. Immunohistochemistry assay of PRL in the anterior pituitary glands showedthat most lactotrophs were located within the lateral wings superior border of theanterior pituitary. Tissues where somatotrophs or lactotrophs were located were dicedinto small pieces at less than1mm3and incubated in CMF-HBSS containing0.3%Itype collagenase,0.1%hyaluronidase, and0.1‰Dnase. After6d in culture, theDCAPCs displayed a monolayer, cobblestone, epithelial-like morphology which arethe typical characteristics of the anterior pituitary cells. GH or PRL immunoreactivitywas present in DCAPCs. Therefore, this model can be used successfully for the study of the mechanisms of hypothalamic factors, peripheral hormones, cytokines, ordietary nutrients regulating GH or PRL synthesis and release.
SCFAs bind to GPR41/43and lead to dissociation of heterotrimeric G proteincomplex into Gαiand βγ subunit, thereby inhibiting adenylyl cyclase(AC) activity.Inactivated AC results in a decrease of intracellular cAMP levels and a subsequentreduction in protein kinase A (PKA) activity. Inhibition of PKA activity inhibitscAMP response element binding protein (CREB) phosphorylation, thereby leading toa decrease of bovine GH gene transcription. The change of the phosphorylation levelsof CREB may decrease the phosphorylated CREB binding protein (CBP) or CBPcomplex interacts with pituitary specific transcription factor-1(Pit-1) resultantinhibition of transcription of the bovine GH and PRL gene. Consequently, SCFAsinhibit bovine GH and PRL gene transcription in DCAPCs. Moreover, SCFAsdecrease viability of DCAPCs, which may be an important cause for the inhibition ofGH and PRL synthesis or secretion.
BHBA bind to GPR109A and lead to dissociation of heterotrimeric G proteincomplex into Gαiand βγ subunit, thereby inhibiting AC activity. Inactivated ACresults in a decrease of intracellular cAMP levels and a subsequent reduction in PKAactivity and CREB phosphorylation level, thereby leading to a decrease of bovine GHand Pit-1gene transcription. The proximal promoters of the GH and PRL gene includebinding sites for Pit-1, thus, the change of phosphorylation levels of CREB couldchange GH and PRL gene transcription level directly or indirectly. Otherwise, BHBAincreased the expression of monocarboxylate transporter1(MCT1) in DCAPCs. Andour finding demonstrates that BHBA triggers the AMPK pathway resulting in theinhibition of GH translation.
NO is synthesized by nitric oxide synthase (NOS) enzyme group in DCAPCs,which utilizes the semiessential amino acid L-arginine as a substrate. Thearginine-NO pathway induced the increase of intracellular calcium concentration inDCAPCs, which may be an important cause for the increase of GH and PRL synthesisor secretion. Tyrosine was converted to dopamine(DA) by tyrosine hydroxylase (TH).The inhibitory action of tyrosine on PRL secretion is caused by DA biding to the D2receptors on the DCAPCs cell membrane.
In addition, the nutrient-hormone interaction networks regulating milk fat andmilk protein synthesis were constructed. These results will provide scientific basis tofurther study the regulatory mechanisms of cow’s milk fat and protein synthesis andimprove the nutritional quality of cow’s milk.
免疫组织化学法研究发现奶牛腺垂体组织中生长激素分泌细胞主要位于腺垂体侧翼区下缘，而催乳素分泌细胞主要位于腺垂体侧翼区上缘。取腺垂体侧翼区组织块，用含有0.3%I型胶原酶、0.1%透明质酸酶、0.01%DNA酶的无钙镁离子Hanks液消化3h后，获得的垂体细胞接种培养5d后可见形状规则的铺路石样上皮细胞，经免疫组织化学法鉴定可分泌GH和PRL，可以用于进一步试验。
SCFAs可以与DCAPCs中的GPR41/43结合，活化抑制型G蛋白α亚基（inhibitory G protein alpha subunit, Gαi），抑制细胞内腺苷酸环化酶（adenylylcyclase, AC）活性，降低胞内cAMP含量，导致细胞内蛋白激酶A（protein kinaseA, PKA）活性降低，进而降低cAMP反应元件结合蛋白（cAMP response elementbinding protein, CREB）磷酸化水平，最终抑制GH基因转录。而磷酸化的CREB可能通过调节细胞内垂体特异性转录因子-1（pituitary-specific transcription factor-1, Pit-1）活性间接抑制GH和PRL基因转录。100ng/L剂量的百日咳毒素（pertussis toxin, PTX）预处理DCAPCs2h可部分逆转SCFAs的上述作用，证实SCFAs可以通过cAMP/PKA/CREB通路调节牛GH和PRL基因表达。此外，SCFAs可降低DCAPCs的细胞活性，这也是导致GH和PRL分泌量减少的原因之一。
BHBA可以通过与DCAPCs细胞膜上的GPR109A相结合，激活Gαi蛋白，抑制AC的酶活性，下调胞内cAMP含量，降低PKA活性和CREB磷酸化水平，最终抑制GH的转录，并通过抑制Pit-1的合成来间接降低GH和PRL表达。此外，BHBA可以刺激MCT1的表达，活化低糖或无糖培养的DCAPCs中AMPK分子，并可能通过抑制mTOR功能减少GH和PRL mRNA的翻译，导致GH和PRL分泌量减少。
精氨酸可在一氧化氮合成酶（nitric oxide synthase, NOS）的催化作用下生成NO，促进细胞外Ca2+内流，进而调节DCAPCs中GH和PRL的合成与分泌，且50-75mg/L的精氨酸促进GH、PRL合成与分泌效果最佳。酪氨酸可在酪氨酸羟化酶（tyrosine hydroxylase, TH）催化作用下代谢为多巴胺，并以自分泌或旁分泌的方式抑制DCAPCs中PRL合成和分泌。
此外，本研究还借鉴相关研究资料和方法，初步构建了调控乳脂肪和乳蛋白合成的营养与激素相互作用网络，以期为深入研究乳脂肪和乳蛋白合成调控机制和改善牛奶营养品质提供科学依据。
Low nutritional quality of cow’s milk has increasingly become a severechallenge faced by the healthy development of dairy industry in China. Milk fat andprotein are the main substances to determine the nutritional quality of cow’s milk.Cow’s milk quality could be affected by many factors, where neuroendocrine factorsplay an important regulatory role to fat and protein contents in cow’s milk. Growthhormone (GH) and prolactin (PRL) is the most important hormone for the regulationof milk protein and milk fat synthesis in dairy cows. The concentration of precursorsof milk components in serum may also regulate the GH and PRL synthesis orsecretion in dairy cow anterior pituitary cells (DCAPCs) with direct or indirectmanners. Therefore, the objective of the present experiment was to investigate theeffects and signaling mechanisms of short-chain fatty acids (SCFAs), β-hydroxy-butyric acid (BHBA), arginin, and tyrosine on the GH and PRL synthesis or secretionin DCAPCs cultured in vitro. In addition, the nutrient-hormone interaction networksregulating milk fat and milk protein synthesis were constructed to get a thoroughunderstanding about the effects and molecular mechanisms of neuroendocrine factorson fatty acid and protein synthesis of cow’s milk.
Immunohistochemistry assay of GH in the anterior pituitary glands showed thatmost somatotrophs were located within the lateral wings inferior border of the anteriorpituitary. Immunohistochemistry assay of PRL in the anterior pituitary glands showedthat most lactotrophs were located within the lateral wings superior border of theanterior pituitary. Tissues where somatotrophs or lactotrophs were located were dicedinto small pieces at less than1mm3and incubated in CMF-HBSS containing0.3%Itype collagenase,0.1%hyaluronidase, and0.1‰Dnase. After6d in culture, theDCAPCs displayed a monolayer, cobblestone, epithelial-like morphology which arethe typical characteristics of the anterior pituitary cells. GH or PRL immunoreactivitywas present in DCAPCs. Therefore, this model can be used successfully for the study of the mechanisms of hypothalamic factors, peripheral hormones, cytokines, ordietary nutrients regulating GH or PRL synthesis and release.
SCFAs bind to GPR41/43and lead to dissociation of heterotrimeric G proteincomplex into Gαiand βγ subunit, thereby inhibiting adenylyl cyclase(AC) activity.Inactivated AC results in a decrease of intracellular cAMP levels and a subsequentreduction in protein kinase A (PKA) activity. Inhibition of PKA activity inhibitscAMP response element binding protein (CREB) phosphorylation, thereby leading toa decrease of bovine GH gene transcription. The change of the phosphorylation levelsof CREB may decrease the phosphorylated CREB binding protein (CBP) or CBPcomplex interacts with pituitary specific transcription factor-1(Pit-1) resultantinhibition of transcription of the bovine GH and PRL gene. Consequently, SCFAsinhibit bovine GH and PRL gene transcription in DCAPCs. Moreover, SCFAsdecrease viability of DCAPCs, which may be an important cause for the inhibition ofGH and PRL synthesis or secretion.
BHBA bind to GPR109A and lead to dissociation of heterotrimeric G proteincomplex into Gαiand βγ subunit, thereby inhibiting AC activity. Inactivated ACresults in a decrease of intracellular cAMP levels and a subsequent reduction in PKAactivity and CREB phosphorylation level, thereby leading to a decrease of bovine GHand Pit-1gene transcription. The proximal promoters of the GH and PRL gene includebinding sites for Pit-1, thus, the change of phosphorylation levels of CREB couldchange GH and PRL gene transcription level directly or indirectly. Otherwise, BHBAincreased the expression of monocarboxylate transporter1(MCT1) in DCAPCs. Andour finding demonstrates that BHBA triggers the AMPK pathway resulting in theinhibition of GH translation.
NO is synthesized by nitric oxide synthase (NOS) enzyme group in DCAPCs,which utilizes the semiessential amino acid L-arginine as a substrate. Thearginine-NO pathway induced the increase of intracellular calcium concentration inDCAPCs, which may be an important cause for the increase of GH and PRL synthesisor secretion. Tyrosine was converted to dopamine(DA) by tyrosine hydroxylase (TH).The inhibitory action of tyrosine on PRL secretion is caused by DA biding to the D2receptors on the DCAPCs cell membrane.
In addition, the nutrient-hormone interaction networks regulating milk fat andmilk protein synthesis were constructed. These results will provide scientific basis tofurther study the regulatory mechanisms of cow’s milk fat and protein synthesis andimprove the nutritional quality of cow’s milk.
引文
[1]文静，卜登攀，王建发，孙鹏.激素调控乳蛋白合成的作用及其分子机制[J].华北农学报，2012,27:111-115.
[2]文静.两种典型日粮模式对奶牛泌乳量、乳品质及泌乳相关激素的影响[D].长春：吉林大学，2013.
[3] ALI CS, KHALIQ T, SARWAR M, et al. Effect of various non protein nitrogensources on in vitro dry matter digestibility, ammonia production, microbialgrowth and pH changes by rumen bacteria[J]. Pakistan Vet J,2008,28:25-30.
[4] LARSON BL. Lactation[M]. Iowa: Iowa State University Press,1985.
[5] BRAMANTI E, SORTINO C, ONOR M, et al. Separation and determination ofdenatured alpha(s1)-, alpha(s2)-, beta-and kappa-caseins by hydrophobicinteraction chromatography in cows', ewes' and goats' milk, milk mixtures andcheeses[J]. J Chromatogr A,2003,994(1-2):59-74.
[6] LAW AJR. Heat denaturation of bovine, caprine, and ovine whey proteins[J].Milchwissenschaft,1995,50:384-388.
[7]李庆章主编.乳腺发育与泌乳生物学[M].北京：科学出版社，2009:95-96.
[8] MEPHAM TB, GAYE P, MARTIN P, et al. Advanced Dairy ChemistryVol1:Proteins [M]. Oxford: Elsevier Press,1992:491-543.
[9] MAAS JA, FRANCE J, MCBRIDE BW. Model of milk protein synthesis.amechanistic model of milk protein synthesis in the lactating bovine mammarygland[J]. J theor Biol,1997,187:252-267.
[10] SHENNAN DB, MILLAR ID, CALVERT DT. Mammary tissue amino acidtransport systems[J]. Proc Nutr Soc,1997,56:177-191.
[11] SHENNAN DB, PEAKER M. Transport of milk constituents by the mammarygland[J]. Physiol Res,2000,80(3):925-951.
[12]何庆华，孔祥峰，吴永宁，等.氨基酸转运载体研究进展[J].氨基酸和生物资源，2007，29(2):40-45.
[13] SHENNAN DB. Mammary gland membrane transport systems[J]. J MammaryGland Biol Neoplasia,1998,3:247-258.
[14] NICHOLS JR, SCHINGOETHE DJ, MAIGA HA, et al. Evaluation of corndistillers grains and ruminally protected lysine and methionine for lactating dairycows[J]. J Dairy Sci,1998,81:482-491.
[15] CELINE J, ALAIN B, MARC F, et al. Evidence for multiple signaling pathwaysin the regulation of gene expression by amino acid in human cell lines[J]. J Nutr,2000,130:1555-1560.
[16] APPUHAMY RN. Regulatory roles of essential amino acids, energy, and insulinin mammary cell protein synthesis[D]. Virginia: Virginia Polytechnic Instituteand State University,2010.
[17] PROUD CG. Regulation of protein synthesis by insulin[J]. Biochemical Societytransactions,2006,34(Pt2):213-216.
[18] PIWIEN PG, VAN MD, ROSS SE, et al. Growth hormone regulatesphosphorylation and function of CCAAT/enhancer-binding protein beta bymodulating Akt and glycogen synthase kinase-3[J]. J Biol Chem,2001,276(22):19664-19671.
[19] BEUGNET A, TEE AR, TAYLOR PM, et al. Regulation of targets of mTORsignalling by intra-cellular amino acid availability[J]. Biochem J,2003,372:555-566.
[20] HAYASHI AA. Regulation of protein synthesis in the mammary gland: athesis[D]. Palmerston North: Massey University,2007.
[21] VINA J, PUERTES IR, SAEZ GT, et al. Role of prolactin in amino acid uptakeby the lactating mammary gland of the rat[J]. FEBS Lett,1981,126:250-252.
[22] SHENNAN DB, MCNEILLIE SA. Milk accumulation down regulates aminoacid uptake via systems A and L by lactating mammary tissue[J]. Horm MetabRes,1994,26:565-618.
[23] ROHA SG, BAIK MG, CHOI YJ, et al. The effect of lactogenic hormones onprotein synthesis and amino acid uptake in rat mammary acinar cell culture atvarious physiological stages[J]. Int J Biochem,1994,26(4):479-485.
[24] RILLEMA JA, GOLDEN K, JENKINS MA. Effect of prolactin onα-aminoisobutyric acid uptake in mouse mammary gland explants[J]. Am JPhysiol Endocrinol Metab,1992,262:402-405.
[25]]MORGAN MY, JAKOBOVITS AW, GORE MB, Wills MR, et al. Serumprolactin in liver disease and its relationship to gynaecomastia[J]. Gut,1978,19(3):170-174.
[26] DEVITO WJ, STONE S.Ethanol inhibits prolactin-induced activation of theJAK/STAT pathway in cultured astrocytes[J]. J Cell Biochem,1999,74(2):278-291.
[27] FRASOR J, BARKAI U, ZHONG L,et al. PRL-induced ERalpha geneexpression is mediated by Janus kinase2(Jak2) while signal transducer andactivator of transcription5b (Stat5b) phosphorylation involves Jak2and a secondtyrosine kinase[J]. Mol Endocrinol,2001,15(11):1941-1952.
[28]王俊锋，黄静，梁国义.泌乳反刍动物乳蛋白的合成机理及调控途径的研究[J].中国乳业，2005，2:24-27.
[29] BARASH I. Prolactin and insulin synergize to regulate the translation modulatorPHAS-I via mitogen-activated protein kinase-independent but wortmannin-andrapamycin-sensitive pathway[J]. Mol Cell Endocrinol,1999,155:37-49.
[30] REDPATH NT, PRICE NT, PROUD CG. Cloning and expression of cDNAencoding protein synthesis elongation factor-2kinase[J]. J Biol Chem,1996,271:17547-17554.
[31] MELMED S. Acromegaly pathogenesis and treatment[J]. J Clin Invest,2009,119(11):3189-3202.
[32] FLINT DJ, GARDNERL M. Evidence that growth hormone stimulates milksynthesis by direct action on the mammary gland and that prolactin exerts effectson milk secretion by maintenance of mammary deoxyribonucleic acid contentand tight junction status[J]. J Biochem,1994,135(2):1119-1124.
[33] LECLERCQ R, DERLOT E, DUVAL J, et al. Plasmid-mediated resistance tovancomycin and teicoplanin in Enterococcus faecium[J]. N Engl J Med,1988,319(3):157-161.
[34] JANSSON N, GREENWOOD SL, JOHANSSON BR, et al. Leptin stimulatesthe activity of the system a amino acid transporter in human placental villousfragments[J]. J Clin Endocrinol Metab,2003,88(3):1205-1211.
[35]牛淑玲.围产期奶牛干物质摄入减少及脂肪动员的神经内分泌调控机制[D].长春：吉林大学，2005.
[36] BIONAZ M, LOOR JJ. Gene networks driving bovine mammary proteinsynthesis during the lactation cycle[J]. Bioinform Biol Insights,2011,5:83-98.
[37] CZERKAWKI JW. An introduction to rumen studies[M]. New York:Pergamonpress,1986:75-108.
[38]王晓旭.围产期奶牛瘤胃微生物区系的变化及微生态制剂的调控作用[D].长春：吉林大学，2012.
[39]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.
[40] BIONAZ M, LOOR JJ.Gene networks driving bovine milk fat synthesis duringthe lactation cycle[J]. BMC Genomics,2008,9:366.
[41]胡菡，王加启，李发娣，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.
[42] EVERETT L, GALLI A, CRABB D. The role of hepatic peroxisomeproliferator-activated receptors(PPARs) in health and disease[J]. Liver,2000,20(3):191-199.
[43] MANDARD S, MüLLER M, KERSTEN S. Peroxisome proliferator-activatedreceptor alpha target genes[J]. Cell Mol Life Sci,2004,61(4):393-416.
[44] DEVINE JH, EUBANK DW, CLOUTHIER DE, et al. Adipose expression of thephosph-oenolpyruvate carboxykinase promoter requiresperoxisome proliferator-activated receptor gamma and9-cis-retinoic acid receptor binding to anadipocyte-specific enhancerin vivo[J]. J Biol Chem,1999,274:13604-13612.
[45]李心慰.乙酸、非酯化脂肪酸、生长激素和催乳素调控奶牛肝细胞脂代谢的信号机制[D].长春：吉林大学，2013.
[46] OPPI-WILLIAMS C, SUAGEE JK, CORL BA. Regulation of lipid synthesis byLXRα and SREBP1in mammary epithelial cells[J]. J Dairy Sci,2013,96:112-121.
[47] MA LY. Regulatory factors of milk fat synthesis in dairy cows[D]. VirginiaPolytechnic Institute and State University,2012.
[48] ETHERTON TD, BAUMAN DE. The biology of somatotropin in growth andlactation of domestic animals[J]. Physiol Rev,1998,78:745-761.
[49] BAUMAN DE. Bovine somatotropin and lactation: from basic science tocommercial application[J]. Domest Anim Endocrin,1999,17:101-116.
[50] BAUMAN DE, Vernon RG. Effects of exogenous bovine somatotropin onlactation [J]. Ann Rev Nutr,1993,13:437-461.
[51] MAO J, MOLENAAR AJ, WHEELER TT, et al. STAT5binding contributes tolactational stimulation of promoter III expressing the bovine acetyl-CoAcarboxylase alpha-encoding gene in the mammary gland[J]. J Mol Endocrinol,2002,29(1):73-88.
[52] LINHER-MELVILLE K, ZANTINGE S, SANLI T, et al. Establishing arelationship between prolactin and altered fatty acid β-oxidation via carnitinepalmitoyl transferase1in breast cancer cells[J]. BMC Cancer,2011,11:56.
[53] MELMED S. The Pituitary(third edition)[M]. London:Academic press,2011:83-166.
[54] LI WS, LIN HR. The endocrine regulation network of growth hormone synthesisand secretion in fish: Emphasis on the signal integration in somatotropes[J]. SciChina Life Sci,2010,53(4):462-470.
[55] KATOH K, TAKAHASHI T, KOBAYASHI Y, et al. Somatotropic axis andnutrition in young ruminants around weaning time[J]. Asian-Aust J Anim Sci,2007,20:1156-1168.
[56] KNUBEL KH. Identification of a non-classical glucocorticoid-responsiveelement in the5’-flanking region of the chicken growth hormone gene[D].University of Maryland,2010.
[57] FREEMAN ME, KANYICSKA B, LERANT A, et al. Prolactin: structure,function, and regulation of secretion[J]. Physiol Rev,2000,80(4):1523-631.
[58] ZHANG TH, SONG SD, LI LJ, et al. Isolation and charact erization of prolactinmessenger RNA from bovine anterior pituitary glands[J]. Acta Genetica Sinica,1992,19:410-415.
[59]曹新，王强，颜景斌，等.牛催乳素基因组及其cDNA全长序列的分子克隆和分析[J].遗传学报,2002,29(9):768-773.
[60] BERWAER M, MARTIAL JA, DAVIS JR. Characterization of an up-streampromoter directing extrapituitary expression of the human prolactin gene[J]. MolEndocrinol,1994,8(5):635-642.
[61] TIAN CL, YE F, XU TJ, et al. GHRP-6induces CREB phosphorylation andgrowth hormone secretion via a protein kinase cσ-dependent pathway in GH3cells[J]. J Huazhong Unive Sci Technol,2010,30(2):183-187.
[62] VELA J, PéREZ-MILLáN MI, BECU-VILLALOBOS D, et al. Differentkinases regulate activation of voltage-dependent calcium channels bydepolarization in GH3cells [J]. Am J Physiol Cell Physiol,2007,293:C951-C959.
[63] SRIKANT CB, PATEL YC. Receptor binding of somatostatin-28is tissuespecific[J]. Nature,1981,5838(294):259-260.
[64] HATTORI N. Expression, regulation and biological actions of growth hormone(GH) and ghrelin in the immune system[J]. Growth Horm IGF Res,2009,19:187-197.
[65] GR NBERG M, TSOLAKIS AV, MAGNUSSON L, et al. Distribution ofobestatin and ghrelin in human tissues: immunoreactive cells in thegastrointestinal tract, pancreas, and mammary glands[J]. J Histochem Cytochem,2008,56:793-801.
[66] GARCíA A, ALVAREZ CV, SMITH RG, et al. Regulation of Pit-1expression byghrelin and GHRP-6through the GH secretagogue receptor[J]. Mol Endocrinol,2001,15:1484-1495.
[67] BADER MF, DOUSSAU F, CHASSEROT-GOLAZ S, et al. Coupling actin andmembrane dynamics during calcium-regulated exocytosis: a role for Rho andARF GTPases [J]. Biochim Biophys Acta,2004,1742:37-49.
[68]刘亚莉. Leptin对生长激素细胞GH分泌的影响及其机制的研究[D].西安：第四军医大学，2005.
[69] MAIER C, SCHALLER G, BURANYI B, et al. The cholinergic system controlsghrelin release and ghrelin-induced growth hormone release in humans, J ClinEndocrinol Metab,2004,89:4729-4733.
[70] ISHIDA M, MITSUI T, YAMAKAWA K, et al. Involvement of cAMP responseelement binding protein in the regulation of cell proliferation and the prolactinpromoter of lactotrophs in primary culture[J]. Am J Physiol Endocrinol Metab,2007,293(6):E1529-E1537.
[71] BRADFORD AP, CONRAD KE, TRAN PH, rt al. Gutierrez-Hartmann,GHF-1/Pit-1functions as a cellspecific integrator of Ras signaling by targetingthe Ras pathway to a composite Ets-1/GHF-1response element[J]. J Biol Chem,1996,271(40):24639-24648.
[72] ROMANO D, MAGALON K, CIAMPINI A, et al. Differential involvement ofthe Ras and Rap1small GTPases in vasoactive intestinal and pituitary adenylylcyclase activating polypeptides control of the prolactin gene[J]. J Biol Chem,2003,278(51):51386-51394.
[73] JACKSON TA, KOTERWAS DM, MORGAN MA, et al. Fibroblast growthfactors regulate prolactin transcription via an atypical Rac-dependent signalingpathway[J]. Mol Endocrinol,2003,17(10):1921-1930.
[74] SZAWKA RE, RIBEIRO AB, LEITE CM, et al. Kisspeptin regulates prolactinrelease through hypothalamic dopaminergic neurons[J]. Endocrinol,2010,151(7):3247-3257.
[75] LENTS C, HEIDORN N, BARB C, et al. Central and peripheral administrationof kisspeptin activates gonadotropin but not somatotropin secretion inprepubertal gilts[J]. Reprod,2008,135:879-887.
[76] THOMAS G.B, CUMMINS JT, FRANCIS H, et al. Effect of restricted feedingon the relationship between hypophysial portal concentrations of growthhormone (GH)-releasing factor and somatostatin, andjugular concentrations ofGH in ovariectomized ewes[J]. Endocrinol,1991,128:1151-1158.
[77] KATOH K, TAKAHASHI T, KOBAYASHI Y, et al. Somatotropic axis andnutrition in young ruminants around weaning time[J]. Asian-Aust J Anim Sci,2007,20(7):1156-1168.
[78] KUHLA B, ALBRECHT D, BRUCKMAIER R, et al. Proteome andradioimmunoassay analyses of pituitary hormones and proteins in response tofeed restriction of dairy cows[J]. Proteomics,2010,10(24):4491-4500.
[79] YEN PM, TASHJIAN AH. Short chain fatty acids increase prolactin and growthhormone production and alter cell morphology in the GH3strain of rat pituitarycells [J]. Endocrinol,1981,109(1):17-22.
[80] ISHIWATA H, NAGANO M, SASAKI Y, et al. Short-Chain Fatty Acids Inhibitthe Release and Content of Growth Hormone in Anterior Pituitary Cells of theGoat [J].Gen Comp Endocrinol,2000,118:400-406.
[81] ORSKOV H, HANSEN AP, HANSEN HE, et al. Acetate: inhibitor of growthhormone hypersecretion in diabetic and non-diabetic uraemic subjects[J]. ActaEndocrinol,1982,99(4):551-558.
[82] KATO S, SATO K, CHIDA H, et al. Effects of Na-butyrate supplementation inmilk formula on plasma concentrations of GH and insulin, and on rumen papilladevelopment in calves[J]. J Endocrinol,2011,211(3):241-248.
[83] GROSS KL, HARMON DL, MINTON JE, et al. Effects of isoenergetic infusionsof propionate and glucose on portal-drained visceral nutrient flux andconcentrations of hormones in lambs maintained by total intragastric infusion[J].J Anim Sci,1990,68:2566-2574.
[84] OHATA Y, MARUYAMA Y, KATOH K, et al. Growth hormone release inducedby an amino acid mixture from primary cultured anterior pituitary cells ofgoats[J]. Domest Anim Endocrinol,1997,14(2):99-107.
[85] ADRI O M, CHRISMAN CJ, BIELAVSKY M, et al. Arginine increases growthhormone gene expression in rat pituitary and GH3cells[J]. Neuroendocrinol,2004,79(1):26-33.
[86] KUHARA T, IKEDA S, OHNEDA A, et al. Effects of intravenous infusion of17amino acids on the secretion of GH, glucagon, and insulin in sheep[J]. AJP-Endo,1991,260(1):E21-E26.
[87] DE CASTRO BARBOSA T, LOUREN O POYARES L, FABRES MACHADOU, et al. Chronic oral administration of arginine induces GH gene expression andinsulin resistance[J]. Life Sci,2006,79(15):1444-1449.
[88] ESTIENNE MJ, BARD CR. The control of adenohypophysial hormone secretionby amino acids and peptides in swine[J]. Domest Anim Endocrinol,2005,29:34-42.
[89] HARMER CJ, MCTAVISH SF, CLARK L, et al. Tyrosine depletion attenuatesdopamine function in healthy volunteers[J]. Psychopharmacology,2001,154(1):105-111.
[90] KATOH K, OHATA Y, ISHIWATA H. Suppressing effects of short-chain fattyacids on growth hormone (GH)-releasing hormone-induced GH release inisolated anterior pituitary cells of goats[J]. Domest Anim Endocrinol,1999,17(1):85-93.
[91] ISHIWATA H, KATOH K, CHEN C, et al. Suppressing actions of butyrate ongrowth hormone (GH) secretion induced by GH-releasing hormone in ratanterior pituitary cells[J]. Gen Comp Endocrinol,2005,143:222-230.
[92] BROWN AJ, GOLDSWORTHY SM, BARNES AA, et al. The Orphan Gprotein-coupled receptors GPR41and GPR43are activated by propionate andother short chain carboxylic acids[J]. J Biol Chem,2003,278:11312-11319.
[93] TAZOE H, OTOMO Y, KAJI I, et al. Roles of short-chain fatty acids receptors,GPR41and GPR43on colonic functions[J]. J Physiol Pharmacol,2008, S2:251-262.
[94] VILLALOBOS C, NUNFIEZ L, GARCIA-SANCHO J. Mechanisms forstimulation of rat anterior pituitary cells by arginine and other amino acids[J]. JPhysiol,1997,502(2):421-431.
[95] SECONDO A, PANNACCIONE A, CATALDI M, et al. Nitric oxide induces
[Ca2+]i oscillations in pituitary GH3cells: involvement of IDRand ERG K+currents[J]. Am J Physiol Cell Physiol,2006,290(1):233-243.
[96] OLINTO SCF, ADRI O MG, CASTRO-BARBOSA T, et al. Arginine inducesGH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries[J]. Braz J Med Biol Res,2012,45(11):1066-1073.
[97]蒋明玉.口服精氮酸促进长骨线性生长的作用及机制的研究[D].上海：复旦大学，2011.
[98] BEN-JONATHAN N, HNASKO R. Dopamine as a prolactin (PRL) inhibitor[J].Endocr Rev,2001,22(6):724-763.
[99]王凯. IL-6在炎症性肠病大鼠脑、结肠组织中表达及信号转导机制研究[D].长春：吉林大学，2010.
[100] D.L.斯佩克特等著，黄培堂译.细胞实验指南[M].北京：科学出版社，2001：432-439.
[101] LISOWSKI P, PIERZCHA M, GOOECIK J. Evaluation of reference genes forstudies of gene expression in the bovine liver, kidney, pituitary, and thyroid[J]. JAppl Genet,2008,49(4):367-372.
[102] BUSTIN SA, BENES V, GARSON JA, et al. The MIQE guidelines: minimuminformation for publication of quantitative real-time PCR experiments[J]. ClinChem,2009,55:4611-4622.
[103] INGRAM CD, KEEFE PD, WOODING FBP, et al. Morphologicalcharacterisation of lactotrophs separated from the bovine pituitary by a rapidenrichment technique. Cell Tissue Res,1988,252:655-659.
[104] ZARZYNSKA J, GAJEWSKA M, MOTYL T. Effects of hormones and growthfactors on TGF-β1expression in bovine mammary epithelial cells[J]. J Dairy Res,2005,72:39-48.
[105] MURATA T, YING SY. Transforming growth factor-beta and activin inhibitbasal secretion of prolactin in a pituitary monolayer culture system[J]. Proc SocExp Biol Med,1991,198:599-605.
[106] FARROW KN, GUTIERREZ-HARTMANN A. Transforming growth factorbeta1inhibits rat prolactin promoter activity in GH4neuroendocrine cells[J].DNA Cell Biol,1999,18:863-873.
[107] TIZARD IR. Veterinary immunology(Ninth edition)[M]. St. Louis:ElsevierPress,2011:146.
[108] VANKELECOM H, CARMELIET P, HEREMANS H, et al. Interferon-gammainhibits stimulated adrenocorticotropin, prolactin, and growth hormone secretionin normal rat anterior pituitary cell cultures[J]. Endocrinology,1990,126:2919-2926.
[109] GONG FY, DENG JY, SHI YF. IFN-γ increases the hGH gene promoter activityin rat GH3cells[J]. Horm Res,2003,60:14-20.
[110] SUTTON JD, DHANOA M, MORANT SV, et al. Rates of production of acetate,propionate, and butyrate in the rumen of lactating dairy cows given normal andlow-roughage diets[J]. J Dairy Sci,2003,86:3620-3633.
[111] VINOLO MA, RODRIGUES HG, NACHBAR RT, et al. Regulation ofinflammation by short chain fatty acids[J]. Nutrients,2011,3:858-876.
[112] BLOTTIèRE HM, BUECHER B, GALMICHE JP, et al. Molecular analysis ofthe effect of short-chain fatty acids on intestinal cell proliferation[J]. Proc NutrSoc,2003,62:101-106.
[113] MINEO H, HASHIZUME Y, HANAKI Y, et al. Chemical specificity ofshort-chain fatty acids in stimulating insulin and glucagon secretion in sheep[J].Am J Physiol,1994,267:E234-241.
[114] ZHAO GY, SUN YB. Effects of volatile fatty acids on IGF-I, IGFBP-3, GH,insulin and glucagon in plasma, and IGF-I and IGFBP-3in different tissues ofgrowing sheep nourished by total intragastric infusions[J]. Asian-Aust J AnimSci,2010,23:366-371.
[115] MATSUNAGA N, KUBOTA I, ROH SG, et al. Effect of mesenteric venousvolatile fatty acids (VFA) infusion on GH secretion in sheep[J]. Endocr J,1997,44:707-714.
[116] MATSUNAGA N, ARAKAWA NT, GOKA T, et al. Effects of ruminal infusionof volatile fatty acids on plasma concentration of growth hormone and insulin insheep[J]. Domest Anim Endocrinol,1999,17:17-27.
[117] MATSUNAGA N, GOKA T, NAM KT, et al. Inhibition of GH releasing factor(GRF)-induced GH secretion by intraruminal infusion of volatile fatty acids(VFA) in sheep[J]. Endocr J,1997,44:133-140.
[118] WANG A, GU Z, HEID B, et al. Identification and characterization of thebovine G protein-coupled receptor GPR41and GPR43genes[J]. J Dairy Sci,2009,92:2696-2705.
[119] GAIDDON C, TIAN J, LOEFFLER JP, et al. Constitutively active G(S)alpha-subunits stimulate Pit-1promoter activity via a protein kinase A-mediatedpathway acting through deoxyribonucleic acid binding sites both for Pit-1and foradenosine3',5'-monophosphate response element-binding protein[J]. Endocrinol,1996,137:1286-1291.
[120] WEHRENS XH, LEHNART SE, REIKEN S, et al. Ryanodine receptor/calciumrelease channel PKA phosphorylation: a critical mediator of heart failureprogression[J]. Proc Natl Acad Sci USA,2006,103:511-518.
[121] MANGMOOL S, KUROSE H. Gi/o protein-dependent and-independentactions of pertussis toxin (PTX)[J]. Toxins,2011,3:884-899.
[122] BRüCKENER KE, EL BAY A, GALLA HJ, et al. Permeabilization in acerebral endothelial barrier model by pertussis toxin involves the PKC effectorpathway and is abolished by elevated levels of cAMP[J]. J Cell Sci,2003,116:1837-1846.
[123] TOPPING DL, CLIFTON PM. Short-chain fatty acids and human colonicfunction: roles of resistant starch and nonstarch polysaccharides[J]. PhysiologicalRev,2001,81:1031-1064.
[124] GIBSON GR, ROBERFROID MB. Dietary modulation of the human colonicmicrobiota: introducing the concept of prebiotics[J]. J Nutr,1995,125:1401-1412.
[125] PAN XD, CHEN FQ, WU TX, et al. Prebiotic oligosaccharides change theconcentrations of short-chain fatty acids and the microbial population of mousebowel[J]. J Zhejiang Univ Sci B,2009,10:258-263.
[126]江振然. G蛋白偶联受体及其功能预测研究[D].武汉：华中科技大学，2007.
[127] THOMSEN W, FRAZER J, UNETT D. Functional assays for screening GPCRtargets[J]. Curr Opin Biotechnol,2005,16:655-665.
[128] LI H, WONG WS. Pertussis toxin activates tyrosine kinase signaling cascade inmyelomonocytic cells: a mechanism for cell adhesion[J]. Biochem Biophys ResCommun,2001,283:1077-1082.
[129] WANG ZY, YANG D, CHEN Q, et al. Induction of dendritic cell maturation bypertussis toxin and its B subunit differentially initiate Toll-like receptor4-dependent signal transduction pathways[J]. Exp Hematol,2006,34:1115-1124.
[130] MELIEN O, SANDNES D, JOHANSEN EJ, et al. Effects of pertussis toxin onextracellular signal-regulated kinase activation in hepatocytes by hormones andreceptor-independent agents: evidence suggesting a stimulatory role of G(i)proteins at a level distal to receptor coupling[J]. J Cell Physiol,2000,184:27-36.
[131] XIONG Y, MIYAMOTO N, SHIBATA K, et al. Short-chain fatty acids stimulateleptin production in adipocytes through the G protein-coupled receptorGPR41[J].Proc Natl Acad Sci USA,2004,101(4):1045-1050.
[132] JEAN A, GUTIERREZ-HARTMANN A, DUVAL DL. A Pit-1threonine220phosphomimic reduces binding to monomeric DNA sites to inhibit Ras andestrogen stimulation of the prolactin gene promoter[J]. Mol Endocrinol,2010,24:91-103.
[133] KAPILOFF MS, FARKASH Y, WEGNER M, et al. Variable effects ofphosphorylation of Pit-1dictated by the DNA response elements[J]. Science,1991,253:786-789.
[134] CAELLES C, HENNEMANN H, KARIN M. M-phase-specific phosphory-lation of the POU transcription factor GHF-1by a cell cycle-regulated proteinkinase inhibits DNA binding[J]. Mol Cell Biol,1995,15:6694-6701.
[135] COHEN LE, HASHIMOTO Y, ZANGER K, et al. CREB-independentregulation by CBP is a novel mechanism of human growth hormone geneexpression[J]. J Clin Invest,1999,104:1123-1130.
[136] LUNDBLAD JR, KWOK RPS, LAURANCE ME, et al. AdenoviralE1A-associated protein p300as a functional homologue of the transcriptionalco-activator CBP[J]. Nature,1995,374:85-88.
[137] TANG Y, CHEN Y, JIANG H, et al. The role of short-chain fatty acids inorchestrating two types of programmed cell death in colon cancer[J]. Autophagy,2011,7(2):235-237.
[138]文静，付守鹏，柳巨雄. β-羟丁酸对中枢神经系统的作用及机制研究进展[J].中国畜牧兽医，2012，39(2):106-110.
[139] SATO H, KUROSAWA T, OIKAWA S. Acetic acid and3-hydroxybutyric acidlevels in cerebrospinal fluid of cattle[J]. Animal Science Journal,2002,73:137-141.
[140] OETZEL GR. Herd-level ketosis–diagnosis and risk factors[C]. AmericanAssociation of Bovine Practitioners40thAnnual Conference, Canada: Vancouver,2007.
[141] QUABBE HJ, BUMKE-VOGT C, IGLESIAS-ROZAS JR, et al. Hypothalamicmodulation of growth hormone secretion in the rhesus monkey: evidence fromintracerebroventricular infusions of glucose, free fatty acid, and ketone bodies[J].J Clin Endocrinol Metab,1991,73(4):765-770.
[142] BOADO R, COLOMBO O, ZANINOVICH AA. Effects of diabetes,beta-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis inthe rat[J]. J Endocrinol Invest,1985,8(2):107-111.
[143] REYNAERT R, TOP W, PEETERS G. Bovine serum growth hormone levels inclinical ketosis[J].Vet Rec,1977,101(2):36-37.
[144] KIRAT D, MASUOKA J, HAYASHI H, et al. Monocarboxylate transporter1(MCT1) plays a direct role in short-chain fatty acids absorption in caprinerumen[J]. J Physiol,2006,576:635-647.
[145] KIRAT D, KATO S. Monocarboxylate transporter1(MCT1) mediates transportof short-chain fatty acids in bovine caecum[J]. Exp Physiol,2006,91(5):835-844.
[146] LAEGER T, P HLAND R, METGES CC, et al. The ketone bodyβ-hydroxybutyric acid influences agouti-related peptide expression viaAMP-activated protein kinase in hypothalamic GT1-7cells[J]. J Endocrinol,2012,213(2):193-203.
[147] TAGGART AK, KERO J, GAN X, et al.(D)-beta-Hydroxybutyrate inhibitsadipocyte lipolysis via the nicotinic acid receptor PUMA-G[J]. J Biol Chem,2005,280(29):26649-26652.
[148] OFFERMANNS S. The nicotinic acid receptor GPR109A(HM74A or PUMA-G)as a new therapeutic target[J]. Trends Pharmacol Sci,2006,27(7):384-390.
[149]王建国.围产期健康奶牛与酮病、亚临床低钙血症病牛血液代谢谱的比较与分析[D].长春：吉林大学，2013.
[150] LEBLANC S. Monitoring metabolic health of dairy cattle in the transitionperiod [J]. J Reprod Develop,2010,56(S):29-35.
[151] XU C, XIA C, LIU GW, et al. Construction of competitive reverse transcriptionpolymerase china reaction inter-reference of PC mRNA by intron approach[J].Scientia Agriculture Sinica.2004,7(3):548-552.
[152] KUHLA B. Central regulation of feed intake in early lactation[C]. Internationalsymposium “Nutritional management in early lactation”, Wageningen,Netherlands,2012.
[153] WANG W, FU SP, XUE WJ, et al. Effect of β-hydroxy-butyric acid on culturedrat hypothalamic neurons function in vitro[J]. Acta Physiologica Sinica,2012,64(S1):6-8.
[154] TITGEMEYER EC, MAMEDOVA LK, SPIVEY KS, et al. An unusualdistribution of the niacin receptor in cattle[J]. J Dairy Sci,2011,94(10):4962-4967.
[155] TUNARU S, KERO J, SCHAUB A, et al.PUMA-G and HM74are receptors fornicotinic acid andmediate its anti-lipolytic effect[J]. Nat Med,2003,9(3):352-355.
[156] XUE B, KAHN BB. AMPK integrates nutrient and hormonal signals to regulatefood intake and energy balance through effects in the hypothalamus andperipheral tissues[J]. J Physiol,2006,574(Pt1):73-83.
[157] LIM CT, KOLA B, KORBONITS M. AMPK as a mediator of hormonalsignalling[J]. J Mol Endocrinol,2010,44(2):87-97.
[158] ARAKAWA T, GOTO T, OKADA Y. Effect of ketone body (D-3-hydroxy-butyrate) on neural activity and energy metabolism in hippocampal slices of theadult guinea pig[J]. Neurosci Lett,1991,130:53-56.
[159] BLAZQUEZ C, WOODS A, DE CEBALLOS ML, et al. The AMP activatedprotein kinase is involved in the regulation of ketone body production byastrocytes[J]. J Neurochem,1999,73:1674-1682.
[160] PELLETIER A, CODERRE L. Ketone bodies alter dinitrophenol-inducedglucose uptake through AMPK inhibition and oxidative stress generation in adultcardiomyocytes[J]. Am J Physiol Endocrinol Metab,2007,292:E1325-E1332.
[161] GWINN DM, SHACKELFORD DB, EGAN DF, et al. AMPK phosphorylationof raptor mediates a metabolic checkpoint[J]. Mol Cell,2008,30(2):214-226.
[162] INOKI K, ZHU T, GUAN KL. TSC2mediates cellular energy response tocontrol cell growth and survival[J]. Cell,2003,115(5):577-590.
[163] HUNG CM, GARCIA-HARO L, SPARKS CA, et al. mTOR-dependent cellsurvival mechanisms[J]. Cold Spring Harb Perspect Biol,2012,4(12):a008771.
[164]吴信，印遇龙，伍国耀.功能性氨基酸——精氨酸和精氨酸生素在猪生产中的研究与应用进展[J].饲料与畜牧，2008,8:8-11.
[165] WANG JF, FU SP, LI SN, et al. Analysis of the relationships between precursorsof milk components concentration in serum and milk fat and protein content[C].The11th world conference on animal production, Beijing,2013.
[166]董矜，田亚平，房征宇. L-Arg对Hela细胞增殖的调控作用研究[J].军医进修学院学报，2004,25(2):100-102.
[167]罗海吉，周爱军，吉鸿雁.高温下精氨酸对一氧化氮和细胞增殖的影响[J].中国公共卫生，2005,21(3):304-305.
[168]徐柏林，王梦芝，张兴夫，等.精氨酸水平对奶牛乳腺上皮细胞体外生长及κ-酪蛋白基因表达的影响[J].动物营养学报，2012,24(5):851-857.
[169]周红宇，张士善.酪氨酸药理作用的研究进展[J].中国药理学报，1993,9(4):251-253.
[170] DEMARIA JE, LIVINGSTONE JD, FREEMAN ME. Characterization of thedopamin-ergic input to the pituitary gland throughout the estrous cycle of therat[J]. Neuroendocrinol,1998,67:377-383.
[171] KARUNAKARAN S, RAMACHANDRAN S, COOTHANKANDASWAMY V,et al. SLC6A14(ATB0,+) protein, a highly concentrative and broad specificamino acid transporter, is a novel and effective drug target for treatment ofestrogen receptor-positive breast cancer[J]. J Biol Chem,2011,286(36):31830-31838.
[172] BAES M. Role of adrenergic catecholamines and intercellular communicationsin the regulation of prolactin and growth hormone release from rat pituitary cellsin vitro[D]. PhD Thesis:KULeuven,1986.
[173] JANSSENS K. Characterization of1-adrenergic receptor expression in the ratanterior pituitary[D]. PhD Thesis:KULeuven,2007.
[174] GRATTAN DR. Behavioural significance of prolactin signalling in the centralnervous system during pregnancy and lactation[J]. Reproduction,2002.123:497-506.
[175] BAYET MC, SCHUSSLER N, VERNEY C, et al. Tyrosine-hydroxylaseimmunoreactive fibres in the rat anterior pituitary[J]. Neuroreport,1994,5:1505-1508.
[176] SCHUSSLER N, BAYET MC, FRAIN O, et al. Evidence of tyrosinehydroxylase mRNA in the anterior and neurointermediate lobes of female ratpituitary[J]. Biochem Biophys Res Commun,1992,189:1716-1724.
[177]刘明丽.利用血清蛋白质作为台湾红羽土鸡产蛋筛选之策略研究[D].新竹：国立清华大学，2007.
[178] HRISTOV AN, ETTER RP, ROPP JK, et al. Effect of dietary crude protein leveland degradability on ruminal fermentation and nitrogen utilization in lactatingdairy cows[J]. J Anim Sci,2004,82:3219-3229.
[179] SWEET IR, COOK DL, DEJULIO E, et al. Regulation of ATP/ADP inpancreatic islets[J]. Diabetes,2004,53(2):401-409.
[180] MENZIES KK, LEFèVRE C, MACMILLAN KL, et al. Insulin regulates milkprotein synthesis at multiple levels in the bovine mammary gland[J]. Funct IntegrGenomics,2009,9:197-217.
[181] STANLEY S, WYNNE K, MCGOWAN B, et al. Hormonal regulation of foodintake[J]. Physiol Rev,2005,85(4):1131-11358.
[182] LI XW, CHEN H, GUAN Y, et al. Acetic acid activates the AMP-activatedprotein kinase signaling pathway to regulate lipid metabolism in bovinehepatocytes[J]. Plos One,2013, DOI:10.1371/journal.pone.0067880.
[183]付守鹏.乙酸、β-羟丁酸对体外培养的大鼠下丘脑神经细胞功能的影响[D].长春：吉林大学，2012.
[184] CSAPO J, ALBERT CS, LOKI K, et al. Quantitative determination of theprotein of bacterial origin based on D-amino acid contents[J]. Acta UnivSapientiae,2008,1:81-97.
[185] ITOH F, KOMATSU T, KUSHIBIKI S, et al. Effects of ghrelin injection onplasma concentrations of glucose, pancreatic hormones and cortisol in Holsteindairy cattle[J]. Comp Biochem Phys A,2006,143:97-102.
[186] ZHANG W, YU G, HUANG Y, et al. Expression of ghrelin and GHSR-1a inmammary glands of dairy goat during the lactation and the effects of gherlin onregulation of mammary function in vitro[J]. Mol Cell Endocrinol,2013,370(1-2):20-31.
[187] COTA D, PROULX K, SMITH KA, et al. Hypothalamic mTOR signalingregulates food intake[J]. Science,2006,312:927-930.
[2]文静.两种典型日粮模式对奶牛泌乳量、乳品质及泌乳相关激素的影响[D].长春：吉林大学，2013.
[3] ALI CS, KHALIQ T, SARWAR M, et al. Effect of various non protein nitrogensources on in vitro dry matter digestibility, ammonia production, microbialgrowth and pH changes by rumen bacteria[J]. Pakistan Vet J,2008,28:25-30.
[4] LARSON BL. Lactation[M]. Iowa: Iowa State University Press,1985.
[5] BRAMANTI E, SORTINO C, ONOR M, et al. Separation and determination ofdenatured alpha(s1)-, alpha(s2)-, beta-and kappa-caseins by hydrophobicinteraction chromatography in cows', ewes' and goats' milk, milk mixtures andcheeses[J]. J Chromatogr A,2003,994(1-2):59-74.
[6] LAW AJR. Heat denaturation of bovine, caprine, and ovine whey proteins[J].Milchwissenschaft,1995,50:384-388.
[7]李庆章主编.乳腺发育与泌乳生物学[M].北京：科学出版社，2009:95-96.
[8] MEPHAM TB, GAYE P, MARTIN P, et al. Advanced Dairy ChemistryVol1:Proteins [M]. Oxford: Elsevier Press,1992:491-543.
[9] MAAS JA, FRANCE J, MCBRIDE BW. Model of milk protein synthesis.amechanistic model of milk protein synthesis in the lactating bovine mammarygland[J]. J theor Biol,1997,187:252-267.
[10] SHENNAN DB, MILLAR ID, CALVERT DT. Mammary tissue amino acidtransport systems[J]. Proc Nutr Soc,1997,56:177-191.
[11] SHENNAN DB, PEAKER M. Transport of milk constituents by the mammarygland[J]. Physiol Res,2000,80(3):925-951.
[12]何庆华，孔祥峰，吴永宁，等.氨基酸转运载体研究进展[J].氨基酸和生物资源，2007，29(2):40-45.
[13] SHENNAN DB. Mammary gland membrane transport systems[J]. J MammaryGland Biol Neoplasia,1998,3:247-258.
[14] NICHOLS JR, SCHINGOETHE DJ, MAIGA HA, et al. Evaluation of corndistillers grains and ruminally protected lysine and methionine for lactating dairycows[J]. J Dairy Sci,1998,81:482-491.
[15] CELINE J, ALAIN B, MARC F, et al. Evidence for multiple signaling pathwaysin the regulation of gene expression by amino acid in human cell lines[J]. J Nutr,2000,130:1555-1560.
[16] APPUHAMY RN. Regulatory roles of essential amino acids, energy, and insulinin mammary cell protein synthesis[D]. Virginia: Virginia Polytechnic Instituteand State University,2010.
[17] PROUD CG. Regulation of protein synthesis by insulin[J]. Biochemical Societytransactions,2006,34(Pt2):213-216.
[18] PIWIEN PG, VAN MD, ROSS SE, et al. Growth hormone regulatesphosphorylation and function of CCAAT/enhancer-binding protein beta bymodulating Akt and glycogen synthase kinase-3[J]. J Biol Chem,2001,276(22):19664-19671.
[19] BEUGNET A, TEE AR, TAYLOR PM, et al. Regulation of targets of mTORsignalling by intra-cellular amino acid availability[J]. Biochem J,2003,372:555-566.
[20] HAYASHI AA. Regulation of protein synthesis in the mammary gland: athesis[D]. Palmerston North: Massey University,2007.
[21] VINA J, PUERTES IR, SAEZ GT, et al. Role of prolactin in amino acid uptakeby the lactating mammary gland of the rat[J]. FEBS Lett,1981,126:250-252.
[22] SHENNAN DB, MCNEILLIE SA. Milk accumulation down regulates aminoacid uptake via systems A and L by lactating mammary tissue[J]. Horm MetabRes,1994,26:565-618.
[23] ROHA SG, BAIK MG, CHOI YJ, et al. The effect of lactogenic hormones onprotein synthesis and amino acid uptake in rat mammary acinar cell culture atvarious physiological stages[J]. Int J Biochem,1994,26(4):479-485.
[24] RILLEMA JA, GOLDEN K, JENKINS MA. Effect of prolactin onα-aminoisobutyric acid uptake in mouse mammary gland explants[J]. Am JPhysiol Endocrinol Metab,1992,262:402-405.
[25]]MORGAN MY, JAKOBOVITS AW, GORE MB, Wills MR, et al. Serumprolactin in liver disease and its relationship to gynaecomastia[J]. Gut,1978,19(3):170-174.
[26] DEVITO WJ, STONE S.Ethanol inhibits prolactin-induced activation of theJAK/STAT pathway in cultured astrocytes[J]. J Cell Biochem,1999,74(2):278-291.
[27] FRASOR J, BARKAI U, ZHONG L,et al. PRL-induced ERalpha geneexpression is mediated by Janus kinase2(Jak2) while signal transducer andactivator of transcription5b (Stat5b) phosphorylation involves Jak2and a secondtyrosine kinase[J]. Mol Endocrinol,2001,15(11):1941-1952.
[28]王俊锋，黄静，梁国义.泌乳反刍动物乳蛋白的合成机理及调控途径的研究[J].中国乳业，2005，2:24-27.
[29] BARASH I. Prolactin and insulin synergize to regulate the translation modulatorPHAS-I via mitogen-activated protein kinase-independent but wortmannin-andrapamycin-sensitive pathway[J]. Mol Cell Endocrinol,1999,155:37-49.
[30] REDPATH NT, PRICE NT, PROUD CG. Cloning and expression of cDNAencoding protein synthesis elongation factor-2kinase[J]. J Biol Chem,1996,271:17547-17554.
[31] MELMED S. Acromegaly pathogenesis and treatment[J]. J Clin Invest,2009,119(11):3189-3202.
[32] FLINT DJ, GARDNERL M. Evidence that growth hormone stimulates milksynthesis by direct action on the mammary gland and that prolactin exerts effectson milk secretion by maintenance of mammary deoxyribonucleic acid contentand tight junction status[J]. J Biochem,1994,135(2):1119-1124.
[33] LECLERCQ R, DERLOT E, DUVAL J, et al. Plasmid-mediated resistance tovancomycin and teicoplanin in Enterococcus faecium[J]. N Engl J Med,1988,319(3):157-161.
[34] JANSSON N, GREENWOOD SL, JOHANSSON BR, et al. Leptin stimulatesthe activity of the system a amino acid transporter in human placental villousfragments[J]. J Clin Endocrinol Metab,2003,88(3):1205-1211.
[35]牛淑玲.围产期奶牛干物质摄入减少及脂肪动员的神经内分泌调控机制[D].长春：吉林大学，2005.
[36] BIONAZ M, LOOR JJ. Gene networks driving bovine mammary proteinsynthesis during the lactation cycle[J]. Bioinform Biol Insights,2011,5:83-98.
[37] CZERKAWKI JW. An introduction to rumen studies[M]. New York:Pergamonpress,1986:75-108.
[38]王晓旭.围产期奶牛瘤胃微生物区系的变化及微生态制剂的调控作用[D].长春：吉林大学，2012.
[39]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.
[40] BIONAZ M, LOOR JJ.Gene networks driving bovine milk fat synthesis duringthe lactation cycle[J]. BMC Genomics,2008,9:366.
[41]胡菡，王加启，李发娣，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.
[42] EVERETT L, GALLI A, CRABB D. The role of hepatic peroxisomeproliferator-activated receptors(PPARs) in health and disease[J]. Liver,2000,20(3):191-199.
[43] MANDARD S, MüLLER M, KERSTEN S. Peroxisome proliferator-activatedreceptor alpha target genes[J]. Cell Mol Life Sci,2004,61(4):393-416.
[44] DEVINE JH, EUBANK DW, CLOUTHIER DE, et al. Adipose expression of thephosph-oenolpyruvate carboxykinase promoter requiresperoxisome proliferator-activated receptor gamma and9-cis-retinoic acid receptor binding to anadipocyte-specific enhancerin vivo[J]. J Biol Chem,1999,274:13604-13612.
[45]李心慰.乙酸、非酯化脂肪酸、生长激素和催乳素调控奶牛肝细胞脂代谢的信号机制[D].长春：吉林大学，2013.
[46] OPPI-WILLIAMS C, SUAGEE JK, CORL BA. Regulation of lipid synthesis byLXRα and SREBP1in mammary epithelial cells[J]. J Dairy Sci,2013,96:112-121.
[47] MA LY. Regulatory factors of milk fat synthesis in dairy cows[D]. VirginiaPolytechnic Institute and State University,2012.
[48] ETHERTON TD, BAUMAN DE. The biology of somatotropin in growth andlactation of domestic animals[J]. Physiol Rev,1998,78:745-761.
[49] BAUMAN DE. Bovine somatotropin and lactation: from basic science tocommercial application[J]. Domest Anim Endocrin,1999,17:101-116.
[50] BAUMAN DE, Vernon RG. Effects of exogenous bovine somatotropin onlactation [J]. Ann Rev Nutr,1993,13:437-461.
[51] MAO J, MOLENAAR AJ, WHEELER TT, et al. STAT5binding contributes tolactational stimulation of promoter III expressing the bovine acetyl-CoAcarboxylase alpha-encoding gene in the mammary gland[J]. J Mol Endocrinol,2002,29(1):73-88.
[52] LINHER-MELVILLE K, ZANTINGE S, SANLI T, et al. Establishing arelationship between prolactin and altered fatty acid β-oxidation via carnitinepalmitoyl transferase1in breast cancer cells[J]. BMC Cancer,2011,11:56.
[53] MELMED S. The Pituitary(third edition)[M]. London:Academic press,2011:83-166.
[54] LI WS, LIN HR. The endocrine regulation network of growth hormone synthesisand secretion in fish: Emphasis on the signal integration in somatotropes[J]. SciChina Life Sci,2010,53(4):462-470.
[55] KATOH K, TAKAHASHI T, KOBAYASHI Y, et al. Somatotropic axis andnutrition in young ruminants around weaning time[J]. Asian-Aust J Anim Sci,2007,20:1156-1168.
[56] KNUBEL KH. Identification of a non-classical glucocorticoid-responsiveelement in the5’-flanking region of the chicken growth hormone gene[D].University of Maryland,2010.
[57] FREEMAN ME, KANYICSKA B, LERANT A, et al. Prolactin: structure,function, and regulation of secretion[J]. Physiol Rev,2000,80(4):1523-631.
[58] ZHANG TH, SONG SD, LI LJ, et al. Isolation and charact erization of prolactinmessenger RNA from bovine anterior pituitary glands[J]. Acta Genetica Sinica,1992,19:410-415.
[59]曹新，王强，颜景斌，等.牛催乳素基因组及其cDNA全长序列的分子克隆和分析[J].遗传学报,2002,29(9):768-773.
[60] BERWAER M, MARTIAL JA, DAVIS JR. Characterization of an up-streampromoter directing extrapituitary expression of the human prolactin gene[J]. MolEndocrinol,1994,8(5):635-642.
[61] TIAN CL, YE F, XU TJ, et al. GHRP-6induces CREB phosphorylation andgrowth hormone secretion via a protein kinase cσ-dependent pathway in GH3cells[J]. J Huazhong Unive Sci Technol,2010,30(2):183-187.
[62] VELA J, PéREZ-MILLáN MI, BECU-VILLALOBOS D, et al. Differentkinases regulate activation of voltage-dependent calcium channels bydepolarization in GH3cells [J]. Am J Physiol Cell Physiol,2007,293:C951-C959.
[63] SRIKANT CB, PATEL YC. Receptor binding of somatostatin-28is tissuespecific[J]. Nature,1981,5838(294):259-260.
[64] HATTORI N. Expression, regulation and biological actions of growth hormone(GH) and ghrelin in the immune system[J]. Growth Horm IGF Res,2009,19:187-197.
[65] GR NBERG M, TSOLAKIS AV, MAGNUSSON L, et al. Distribution ofobestatin and ghrelin in human tissues: immunoreactive cells in thegastrointestinal tract, pancreas, and mammary glands[J]. J Histochem Cytochem,2008,56:793-801.
[66] GARCíA A, ALVAREZ CV, SMITH RG, et al. Regulation of Pit-1expression byghrelin and GHRP-6through the GH secretagogue receptor[J]. Mol Endocrinol,2001,15:1484-1495.
[67] BADER MF, DOUSSAU F, CHASSEROT-GOLAZ S, et al. Coupling actin andmembrane dynamics during calcium-regulated exocytosis: a role for Rho andARF GTPases [J]. Biochim Biophys Acta,2004,1742:37-49.
[68]刘亚莉. Leptin对生长激素细胞GH分泌的影响及其机制的研究[D].西安：第四军医大学，2005.
[69] MAIER C, SCHALLER G, BURANYI B, et al. The cholinergic system controlsghrelin release and ghrelin-induced growth hormone release in humans, J ClinEndocrinol Metab,2004,89:4729-4733.
[70] ISHIDA M, MITSUI T, YAMAKAWA K, et al. Involvement of cAMP responseelement binding protein in the regulation of cell proliferation and the prolactinpromoter of lactotrophs in primary culture[J]. Am J Physiol Endocrinol Metab,2007,293(6):E1529-E1537.
[71] BRADFORD AP, CONRAD KE, TRAN PH, rt al. Gutierrez-Hartmann,GHF-1/Pit-1functions as a cellspecific integrator of Ras signaling by targetingthe Ras pathway to a composite Ets-1/GHF-1response element[J]. J Biol Chem,1996,271(40):24639-24648.
[72] ROMANO D, MAGALON K, CIAMPINI A, et al. Differential involvement ofthe Ras and Rap1small GTPases in vasoactive intestinal and pituitary adenylylcyclase activating polypeptides control of the prolactin gene[J]. J Biol Chem,2003,278(51):51386-51394.
[73] JACKSON TA, KOTERWAS DM, MORGAN MA, et al. Fibroblast growthfactors regulate prolactin transcription via an atypical Rac-dependent signalingpathway[J]. Mol Endocrinol,2003,17(10):1921-1930.
[74] SZAWKA RE, RIBEIRO AB, LEITE CM, et al. Kisspeptin regulates prolactinrelease through hypothalamic dopaminergic neurons[J]. Endocrinol,2010,151(7):3247-3257.
[75] LENTS C, HEIDORN N, BARB C, et al. Central and peripheral administrationof kisspeptin activates gonadotropin but not somatotropin secretion inprepubertal gilts[J]. Reprod,2008,135:879-887.
[76] THOMAS G.B, CUMMINS JT, FRANCIS H, et al. Effect of restricted feedingon the relationship between hypophysial portal concentrations of growthhormone (GH)-releasing factor and somatostatin, andjugular concentrations ofGH in ovariectomized ewes[J]. Endocrinol,1991,128:1151-1158.
[77] KATOH K, TAKAHASHI T, KOBAYASHI Y, et al. Somatotropic axis andnutrition in young ruminants around weaning time[J]. Asian-Aust J Anim Sci,2007,20(7):1156-1168.
[78] KUHLA B, ALBRECHT D, BRUCKMAIER R, et al. Proteome andradioimmunoassay analyses of pituitary hormones and proteins in response tofeed restriction of dairy cows[J]. Proteomics,2010,10(24):4491-4500.
[79] YEN PM, TASHJIAN AH. Short chain fatty acids increase prolactin and growthhormone production and alter cell morphology in the GH3strain of rat pituitarycells [J]. Endocrinol,1981,109(1):17-22.
[80] ISHIWATA H, NAGANO M, SASAKI Y, et al. Short-Chain Fatty Acids Inhibitthe Release and Content of Growth Hormone in Anterior Pituitary Cells of theGoat [J].Gen Comp Endocrinol,2000,118:400-406.
[81] ORSKOV H, HANSEN AP, HANSEN HE, et al. Acetate: inhibitor of growthhormone hypersecretion in diabetic and non-diabetic uraemic subjects[J]. ActaEndocrinol,1982,99(4):551-558.
[82] KATO S, SATO K, CHIDA H, et al. Effects of Na-butyrate supplementation inmilk formula on plasma concentrations of GH and insulin, and on rumen papilladevelopment in calves[J]. J Endocrinol,2011,211(3):241-248.
[83] GROSS KL, HARMON DL, MINTON JE, et al. Effects of isoenergetic infusionsof propionate and glucose on portal-drained visceral nutrient flux andconcentrations of hormones in lambs maintained by total intragastric infusion[J].J Anim Sci,1990,68:2566-2574.
[84] OHATA Y, MARUYAMA Y, KATOH K, et al. Growth hormone release inducedby an amino acid mixture from primary cultured anterior pituitary cells ofgoats[J]. Domest Anim Endocrinol,1997,14(2):99-107.
[85] ADRI O M, CHRISMAN CJ, BIELAVSKY M, et al. Arginine increases growthhormone gene expression in rat pituitary and GH3cells[J]. Neuroendocrinol,2004,79(1):26-33.
[86] KUHARA T, IKEDA S, OHNEDA A, et al. Effects of intravenous infusion of17amino acids on the secretion of GH, glucagon, and insulin in sheep[J]. AJP-Endo,1991,260(1):E21-E26.
[87] DE CASTRO BARBOSA T, LOUREN O POYARES L, FABRES MACHADOU, et al. Chronic oral administration of arginine induces GH gene expression andinsulin resistance[J]. Life Sci,2006,79(15):1444-1449.
[88] ESTIENNE MJ, BARD CR. The control of adenohypophysial hormone secretionby amino acids and peptides in swine[J]. Domest Anim Endocrinol,2005,29:34-42.
[89] HARMER CJ, MCTAVISH SF, CLARK L, et al. Tyrosine depletion attenuatesdopamine function in healthy volunteers[J]. Psychopharmacology,2001,154(1):105-111.
[90] KATOH K, OHATA Y, ISHIWATA H. Suppressing effects of short-chain fattyacids on growth hormone (GH)-releasing hormone-induced GH release inisolated anterior pituitary cells of goats[J]. Domest Anim Endocrinol,1999,17(1):85-93.
[91] ISHIWATA H, KATOH K, CHEN C, et al. Suppressing actions of butyrate ongrowth hormone (GH) secretion induced by GH-releasing hormone in ratanterior pituitary cells[J]. Gen Comp Endocrinol,2005,143:222-230.
[92] BROWN AJ, GOLDSWORTHY SM, BARNES AA, et al. The Orphan Gprotein-coupled receptors GPR41and GPR43are activated by propionate andother short chain carboxylic acids[J]. J Biol Chem,2003,278:11312-11319.
[93] TAZOE H, OTOMO Y, KAJI I, et al. Roles of short-chain fatty acids receptors,GPR41and GPR43on colonic functions[J]. J Physiol Pharmacol,2008, S2:251-262.
[94] VILLALOBOS C, NUNFIEZ L, GARCIA-SANCHO J. Mechanisms forstimulation of rat anterior pituitary cells by arginine and other amino acids[J]. JPhysiol,1997,502(2):421-431.
[95] SECONDO A, PANNACCIONE A, CATALDI M, et al. Nitric oxide induces
[Ca2+]i oscillations in pituitary GH3cells: involvement of IDRand ERG K+currents[J]. Am J Physiol Cell Physiol,2006,290(1):233-243.
[96] OLINTO SCF, ADRI O MG, CASTRO-BARBOSA T, et al. Arginine inducesGH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries[J]. Braz J Med Biol Res,2012,45(11):1066-1073.
[97]蒋明玉.口服精氮酸促进长骨线性生长的作用及机制的研究[D].上海：复旦大学，2011.
[98] BEN-JONATHAN N, HNASKO R. Dopamine as a prolactin (PRL) inhibitor[J].Endocr Rev,2001,22(6):724-763.
[99]王凯. IL-6在炎症性肠病大鼠脑、结肠组织中表达及信号转导机制研究[D].长春：吉林大学，2010.
[100] D.L.斯佩克特等著，黄培堂译.细胞实验指南[M].北京：科学出版社，2001：432-439.
[101] LISOWSKI P, PIERZCHA M, GOOECIK J. Evaluation of reference genes forstudies of gene expression in the bovine liver, kidney, pituitary, and thyroid[J]. JAppl Genet,2008,49(4):367-372.
[102] BUSTIN SA, BENES V, GARSON JA, et al. The MIQE guidelines: minimuminformation for publication of quantitative real-time PCR experiments[J]. ClinChem,2009,55:4611-4622.
[103] INGRAM CD, KEEFE PD, WOODING FBP, et al. Morphologicalcharacterisation of lactotrophs separated from the bovine pituitary by a rapidenrichment technique. Cell Tissue Res,1988,252:655-659.
[104] ZARZYNSKA J, GAJEWSKA M, MOTYL T. Effects of hormones and growthfactors on TGF-β1expression in bovine mammary epithelial cells[J]. J Dairy Res,2005,72:39-48.
[105] MURATA T, YING SY. Transforming growth factor-beta and activin inhibitbasal secretion of prolactin in a pituitary monolayer culture system[J]. Proc SocExp Biol Med,1991,198:599-605.
[106] FARROW KN, GUTIERREZ-HARTMANN A. Transforming growth factorbeta1inhibits rat prolactin promoter activity in GH4neuroendocrine cells[J].DNA Cell Biol,1999,18:863-873.
[107] TIZARD IR. Veterinary immunology(Ninth edition)[M]. St. Louis:ElsevierPress,2011:146.
[108] VANKELECOM H, CARMELIET P, HEREMANS H, et al. Interferon-gammainhibits stimulated adrenocorticotropin, prolactin, and growth hormone secretionin normal rat anterior pituitary cell cultures[J]. Endocrinology,1990,126:2919-2926.
[109] GONG FY, DENG JY, SHI YF. IFN-γ increases the hGH gene promoter activityin rat GH3cells[J]. Horm Res,2003,60:14-20.
[110] SUTTON JD, DHANOA M, MORANT SV, et al. Rates of production of acetate,propionate, and butyrate in the rumen of lactating dairy cows given normal andlow-roughage diets[J]. J Dairy Sci,2003,86:3620-3633.
[111] VINOLO MA, RODRIGUES HG, NACHBAR RT, et al. Regulation ofinflammation by short chain fatty acids[J]. Nutrients,2011,3:858-876.
[112] BLOTTIèRE HM, BUECHER B, GALMICHE JP, et al. Molecular analysis ofthe effect of short-chain fatty acids on intestinal cell proliferation[J]. Proc NutrSoc,2003,62:101-106.
[113] MINEO H, HASHIZUME Y, HANAKI Y, et al. Chemical specificity ofshort-chain fatty acids in stimulating insulin and glucagon secretion in sheep[J].Am J Physiol,1994,267:E234-241.
[114] ZHAO GY, SUN YB. Effects of volatile fatty acids on IGF-I, IGFBP-3, GH,insulin and glucagon in plasma, and IGF-I and IGFBP-3in different tissues ofgrowing sheep nourished by total intragastric infusions[J]. Asian-Aust J AnimSci,2010,23:366-371.
[115] MATSUNAGA N, KUBOTA I, ROH SG, et al. Effect of mesenteric venousvolatile fatty acids (VFA) infusion on GH secretion in sheep[J]. Endocr J,1997,44:707-714.
[116] MATSUNAGA N, ARAKAWA NT, GOKA T, et al. Effects of ruminal infusionof volatile fatty acids on plasma concentration of growth hormone and insulin insheep[J]. Domest Anim Endocrinol,1999,17:17-27.
[117] MATSUNAGA N, GOKA T, NAM KT, et al. Inhibition of GH releasing factor(GRF)-induced GH secretion by intraruminal infusion of volatile fatty acids(VFA) in sheep[J]. Endocr J,1997,44:133-140.
[118] WANG A, GU Z, HEID B, et al. Identification and characterization of thebovine G protein-coupled receptor GPR41and GPR43genes[J]. J Dairy Sci,2009,92:2696-2705.
[119] GAIDDON C, TIAN J, LOEFFLER JP, et al. Constitutively active G(S)alpha-subunits stimulate Pit-1promoter activity via a protein kinase A-mediatedpathway acting through deoxyribonucleic acid binding sites both for Pit-1and foradenosine3',5'-monophosphate response element-binding protein[J]. Endocrinol,1996,137:1286-1291.
[120] WEHRENS XH, LEHNART SE, REIKEN S, et al. Ryanodine receptor/calciumrelease channel PKA phosphorylation: a critical mediator of heart failureprogression[J]. Proc Natl Acad Sci USA,2006,103:511-518.
[121] MANGMOOL S, KUROSE H. Gi/o protein-dependent and-independentactions of pertussis toxin (PTX)[J]. Toxins,2011,3:884-899.
[122] BRüCKENER KE, EL BAY A, GALLA HJ, et al. Permeabilization in acerebral endothelial barrier model by pertussis toxin involves the PKC effectorpathway and is abolished by elevated levels of cAMP[J]. J Cell Sci,2003,116:1837-1846.
[123] TOPPING DL, CLIFTON PM. Short-chain fatty acids and human colonicfunction: roles of resistant starch and nonstarch polysaccharides[J]. PhysiologicalRev,2001,81:1031-1064.
[124] GIBSON GR, ROBERFROID MB. Dietary modulation of the human colonicmicrobiota: introducing the concept of prebiotics[J]. J Nutr,1995,125:1401-1412.
[125] PAN XD, CHEN FQ, WU TX, et al. Prebiotic oligosaccharides change theconcentrations of short-chain fatty acids and the microbial population of mousebowel[J]. J Zhejiang Univ Sci B,2009,10:258-263.
[126]江振然. G蛋白偶联受体及其功能预测研究[D].武汉：华中科技大学，2007.
[127] THOMSEN W, FRAZER J, UNETT D. Functional assays for screening GPCRtargets[J]. Curr Opin Biotechnol,2005,16:655-665.
[128] LI H, WONG WS. Pertussis toxin activates tyrosine kinase signaling cascade inmyelomonocytic cells: a mechanism for cell adhesion[J]. Biochem Biophys ResCommun,2001,283:1077-1082.
[129] WANG ZY, YANG D, CHEN Q, et al. Induction of dendritic cell maturation bypertussis toxin and its B subunit differentially initiate Toll-like receptor4-dependent signal transduction pathways[J]. Exp Hematol,2006,34:1115-1124.
[130] MELIEN O, SANDNES D, JOHANSEN EJ, et al. Effects of pertussis toxin onextracellular signal-regulated kinase activation in hepatocytes by hormones andreceptor-independent agents: evidence suggesting a stimulatory role of G(i)proteins at a level distal to receptor coupling[J]. J Cell Physiol,2000,184:27-36.
[131] XIONG Y, MIYAMOTO N, SHIBATA K, et al. Short-chain fatty acids stimulateleptin production in adipocytes through the G protein-coupled receptorGPR41[J].Proc Natl Acad Sci USA,2004,101(4):1045-1050.
[132] JEAN A, GUTIERREZ-HARTMANN A, DUVAL DL. A Pit-1threonine220phosphomimic reduces binding to monomeric DNA sites to inhibit Ras andestrogen stimulation of the prolactin gene promoter[J]. Mol Endocrinol,2010,24:91-103.
[133] KAPILOFF MS, FARKASH Y, WEGNER M, et al. Variable effects ofphosphorylation of Pit-1dictated by the DNA response elements[J]. Science,1991,253:786-789.
[134] CAELLES C, HENNEMANN H, KARIN M. M-phase-specific phosphory-lation of the POU transcription factor GHF-1by a cell cycle-regulated proteinkinase inhibits DNA binding[J]. Mol Cell Biol,1995,15:6694-6701.
[135] COHEN LE, HASHIMOTO Y, ZANGER K, et al. CREB-independentregulation by CBP is a novel mechanism of human growth hormone geneexpression[J]. J Clin Invest,1999,104:1123-1130.
[136] LUNDBLAD JR, KWOK RPS, LAURANCE ME, et al. AdenoviralE1A-associated protein p300as a functional homologue of the transcriptionalco-activator CBP[J]. Nature,1995,374:85-88.
[137] TANG Y, CHEN Y, JIANG H, et al. The role of short-chain fatty acids inorchestrating two types of programmed cell death in colon cancer[J]. Autophagy,2011,7(2):235-237.
[138]文静，付守鹏，柳巨雄. β-羟丁酸对中枢神经系统的作用及机制研究进展[J].中国畜牧兽医，2012，39(2):106-110.
[139] SATO H, KUROSAWA T, OIKAWA S. Acetic acid and3-hydroxybutyric acidlevels in cerebrospinal fluid of cattle[J]. Animal Science Journal,2002,73:137-141.
[140] OETZEL GR. Herd-level ketosis–diagnosis and risk factors[C]. AmericanAssociation of Bovine Practitioners40thAnnual Conference, Canada: Vancouver,2007.
[141] QUABBE HJ, BUMKE-VOGT C, IGLESIAS-ROZAS JR, et al. Hypothalamicmodulation of growth hormone secretion in the rhesus monkey: evidence fromintracerebroventricular infusions of glucose, free fatty acid, and ketone bodies[J].J Clin Endocrinol Metab,1991,73(4):765-770.
[142] BOADO R, COLOMBO O, ZANINOVICH AA. Effects of diabetes,beta-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis inthe rat[J]. J Endocrinol Invest,1985,8(2):107-111.
[143] REYNAERT R, TOP W, PEETERS G. Bovine serum growth hormone levels inclinical ketosis[J].Vet Rec,1977,101(2):36-37.
[144] KIRAT D, MASUOKA J, HAYASHI H, et al. Monocarboxylate transporter1(MCT1) plays a direct role in short-chain fatty acids absorption in caprinerumen[J]. J Physiol,2006,576:635-647.
[145] KIRAT D, KATO S. Monocarboxylate transporter1(MCT1) mediates transportof short-chain fatty acids in bovine caecum[J]. Exp Physiol,2006,91(5):835-844.
[146] LAEGER T, P HLAND R, METGES CC, et al. The ketone bodyβ-hydroxybutyric acid influences agouti-related peptide expression viaAMP-activated protein kinase in hypothalamic GT1-7cells[J]. J Endocrinol,2012,213(2):193-203.
[147] TAGGART AK, KERO J, GAN X, et al.(D)-beta-Hydroxybutyrate inhibitsadipocyte lipolysis via the nicotinic acid receptor PUMA-G[J]. J Biol Chem,2005,280(29):26649-26652.
[148] OFFERMANNS S. The nicotinic acid receptor GPR109A(HM74A or PUMA-G)as a new therapeutic target[J]. Trends Pharmacol Sci,2006,27(7):384-390.
[149]王建国.围产期健康奶牛与酮病、亚临床低钙血症病牛血液代谢谱的比较与分析[D].长春：吉林大学，2013.
[150] LEBLANC S. Monitoring metabolic health of dairy cattle in the transitionperiod [J]. J Reprod Develop,2010,56(S):29-35.
[151] XU C, XIA C, LIU GW, et al. Construction of competitive reverse transcriptionpolymerase china reaction inter-reference of PC mRNA by intron approach[J].Scientia Agriculture Sinica.2004,7(3):548-552.
[152] KUHLA B. Central regulation of feed intake in early lactation[C]. Internationalsymposium “Nutritional management in early lactation”, Wageningen,Netherlands,2012.
[153] WANG W, FU SP, XUE WJ, et al. Effect of β-hydroxy-butyric acid on culturedrat hypothalamic neurons function in vitro[J]. Acta Physiologica Sinica,2012,64(S1):6-8.
[154] TITGEMEYER EC, MAMEDOVA LK, SPIVEY KS, et al. An unusualdistribution of the niacin receptor in cattle[J]. J Dairy Sci,2011,94(10):4962-4967.
[155] TUNARU S, KERO J, SCHAUB A, et al.PUMA-G and HM74are receptors fornicotinic acid andmediate its anti-lipolytic effect[J]. Nat Med,2003,9(3):352-355.
[156] XUE B, KAHN BB. AMPK integrates nutrient and hormonal signals to regulatefood intake and energy balance through effects in the hypothalamus andperipheral tissues[J]. J Physiol,2006,574(Pt1):73-83.
[157] LIM CT, KOLA B, KORBONITS M. AMPK as a mediator of hormonalsignalling[J]. J Mol Endocrinol,2010,44(2):87-97.
[158] ARAKAWA T, GOTO T, OKADA Y. Effect of ketone body (D-3-hydroxy-butyrate) on neural activity and energy metabolism in hippocampal slices of theadult guinea pig[J]. Neurosci Lett,1991,130:53-56.
[159] BLAZQUEZ C, WOODS A, DE CEBALLOS ML, et al. The AMP activatedprotein kinase is involved in the regulation of ketone body production byastrocytes[J]. J Neurochem,1999,73:1674-1682.
[160] PELLETIER A, CODERRE L. Ketone bodies alter dinitrophenol-inducedglucose uptake through AMPK inhibition and oxidative stress generation in adultcardiomyocytes[J]. Am J Physiol Endocrinol Metab,2007,292:E1325-E1332.
[161] GWINN DM, SHACKELFORD DB, EGAN DF, et al. AMPK phosphorylationof raptor mediates a metabolic checkpoint[J]. Mol Cell,2008,30(2):214-226.
[162] INOKI K, ZHU T, GUAN KL. TSC2mediates cellular energy response tocontrol cell growth and survival[J]. Cell,2003,115(5):577-590.
[163] HUNG CM, GARCIA-HARO L, SPARKS CA, et al. mTOR-dependent cellsurvival mechanisms[J]. Cold Spring Harb Perspect Biol,2012,4(12):a008771.
[164]吴信，印遇龙，伍国耀.功能性氨基酸——精氨酸和精氨酸生素在猪生产中的研究与应用进展[J].饲料与畜牧，2008,8:8-11.
[165] WANG JF, FU SP, LI SN, et al. Analysis of the relationships between precursorsof milk components concentration in serum and milk fat and protein content[C].The11th world conference on animal production, Beijing,2013.
[166]董矜，田亚平，房征宇. L-Arg对Hela细胞增殖的调控作用研究[J].军医进修学院学报，2004,25(2):100-102.
[167]罗海吉，周爱军，吉鸿雁.高温下精氨酸对一氧化氮和细胞增殖的影响[J].中国公共卫生，2005,21(3):304-305.
[168]徐柏林，王梦芝，张兴夫，等.精氨酸水平对奶牛乳腺上皮细胞体外生长及κ-酪蛋白基因表达的影响[J].动物营养学报，2012,24(5):851-857.
[169]周红宇，张士善.酪氨酸药理作用的研究进展[J].中国药理学报，1993,9(4):251-253.
[170] DEMARIA JE, LIVINGSTONE JD, FREEMAN ME. Characterization of thedopamin-ergic input to the pituitary gland throughout the estrous cycle of therat[J]. Neuroendocrinol,1998,67:377-383.
[171] KARUNAKARAN S, RAMACHANDRAN S, COOTHANKANDASWAMY V,et al. SLC6A14(ATB0,+) protein, a highly concentrative and broad specificamino acid transporter, is a novel and effective drug target for treatment ofestrogen receptor-positive breast cancer[J]. J Biol Chem,2011,286(36):31830-31838.
[172] BAES M. Role of adrenergic catecholamines and intercellular communicationsin the regulation of prolactin and growth hormone release from rat pituitary cellsin vitro[D]. PhD Thesis:KULeuven,1986.
[173] JANSSENS K. Characterization of1-adrenergic receptor expression in the ratanterior pituitary[D]. PhD Thesis:KULeuven,2007.
[174] GRATTAN DR. Behavioural significance of prolactin signalling in the centralnervous system during pregnancy and lactation[J]. Reproduction,2002.123:497-506.
[175] BAYET MC, SCHUSSLER N, VERNEY C, et al. Tyrosine-hydroxylaseimmunoreactive fibres in the rat anterior pituitary[J]. Neuroreport,1994,5:1505-1508.
[176] SCHUSSLER N, BAYET MC, FRAIN O, et al. Evidence of tyrosinehydroxylase mRNA in the anterior and neurointermediate lobes of female ratpituitary[J]. Biochem Biophys Res Commun,1992,189:1716-1724.
[177]刘明丽.利用血清蛋白质作为台湾红羽土鸡产蛋筛选之策略研究[D].新竹：国立清华大学，2007.
[178] HRISTOV AN, ETTER RP, ROPP JK, et al. Effect of dietary crude protein leveland degradability on ruminal fermentation and nitrogen utilization in lactatingdairy cows[J]. J Anim Sci,2004,82:3219-3229.
[179] SWEET IR, COOK DL, DEJULIO E, et al. Regulation of ATP/ADP inpancreatic islets[J]. Diabetes,2004,53(2):401-409.
[180] MENZIES KK, LEFèVRE C, MACMILLAN KL, et al. Insulin regulates milkprotein synthesis at multiple levels in the bovine mammary gland[J]. Funct IntegrGenomics,2009,9:197-217.
[181] STANLEY S, WYNNE K, MCGOWAN B, et al. Hormonal regulation of foodintake[J]. Physiol Rev,2005,85(4):1131-11358.
[182] LI XW, CHEN H, GUAN Y, et al. Acetic acid activates the AMP-activatedprotein kinase signaling pathway to regulate lipid metabolism in bovinehepatocytes[J]. Plos One,2013, DOI:10.1371/journal.pone.0067880.
[183]付守鹏.乙酸、β-羟丁酸对体外培养的大鼠下丘脑神经细胞功能的影响[D].长春：吉林大学，2012.
[184] CSAPO J, ALBERT CS, LOKI K, et al. Quantitative determination of theprotein of bacterial origin based on D-amino acid contents[J]. Acta UnivSapientiae,2008,1:81-97.
[185] ITOH F, KOMATSU T, KUSHIBIKI S, et al. Effects of ghrelin injection onplasma concentrations of glucose, pancreatic hormones and cortisol in Holsteindairy cattle[J]. Comp Biochem Phys A,2006,143:97-102.
[186] ZHANG W, YU G, HUANG Y, et al. Expression of ghrelin and GHSR-1a inmammary glands of dairy goat during the lactation and the effects of gherlin onregulation of mammary function in vitro[J]. Mol Cell Endocrinol,2013,370(1-2):20-31.
[187] COTA D, PROULX K, SMITH KA, et al. Hypothalamic mTOR signalingregulates food intake[J]. Science,2006,312:927-930.