EFFECTS OF DIFFERENT BREAST PUMPING PROTOCOLS ON ALPHA LACTALBUMIN MRNA CONCE

不同吸奶方案对 α 乳清蛋白 mRNA 浓度的影响

• 批准号: 7605888
• 负责人: MOREY W HAYMOND
• 金额: $ 1万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605888
• 关键词: Academy; Affect; Allergic; American; Apical; Breast; Breast Feeding; Cell membrane; Collection; Computer Retrieval of Information on Scientific Projects Database; Condition; Cytosol; Data; Enzymes; Epithelial Cells; Fasting; Fatty acid glycerol esters; Food; Funding; Gastroenteritis; Genetic Transcription; Glucose; Grant; Hormones; Human; Human Milk; Incidence; Infant; Institution; Lactalbumin; Lactose; Life; Lipids; Mammary gland; Messenger RNA; Milk; Milk Proteins; Molecular; Newborn Infant; Nipples; Numbers; Otitis Media; Oxytocin; Pediatrics; Physiologic pulse; Physiological; Pituitary Gland; Plasma; Policies; Positioning Attribute; Process; Production; Progress Reports; Prolactin; Proteins; Protocols documentation; Pulse taking; Pump; Reflex action; Regulation; Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Source; Thinking; Time; Tracer; Transferase; Translations; United States National Institutes of Health; Variant; Water; Woman; Work; alpha Lactalbumin; base; day; feeding; hormone regulation; in vivo; mammary epithelium; milk fat globule; r-hGH-M; stable isotope; technique development

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HYPOTHESIS Hypotheses: H1: Physiologic increases in prolactin and oxytocin induced by complete emptying of the breast using a breast pump will increase mRNA of alpha-lactalbumen more than frequent small pulses of breast emptying. SPECIFIC AIMS: This protocol will attempt to determine if timing of collection in relation to emptying the breast will affect the mRNA content in milk fat globules (MFG) and to determine the relationship of changes in this mRNA concentrations and the plasma concentrations of prolacting and oxytocin. BACKGROUND AND SIGNIFICANCE: Breast milk is the ideal food for newborn infants and infants who are breast fed have a lower incidence of gastroenteritis, otitis media and a number of allergic conditions (Work Group on Breastfeeding). The American Academy of Pediatrics recommends that infant be fed breast milk for the first 6 mondhs of life and partially fed breast milk for up to 1 year (American Academy of Pediatrics Policy). A number of women struggle with breast feeding and less than 25% of those who attempt it are successful for longer than 1 month. It is assumed that lactose production is a primary regulator of human milk production since it is the primary osmotic agent in milk (Mephan 1987). As opposed to milk proteins and fat, the lactose concentration in milk water is constant from the initiation of a breast-feeding until the end, but is species specific (Davies et al 1983). Over the past several years, we have demonstrated using stable isotope tracers of glucose that 50 to 60% of lactose is derived from maternal plasma glucose but that up to 40 to 50% of lactose in human milk is derived from a process of de novo synthesis of lactose within the mammary epithelium (Sunehag et al 2002, Sunehag et al 2003). The proportion of lactose derived from hexoneogenesis is affected by fasting but not rhGH treatment despite the fact that rhGH increased milk production by 30% (Kaplan et al). The mechanism(s) by which hexoneogenesis and lactose synthesis are controlled is not known in humans. The fat component in human milk appears as a milk fat globule (MFG) (Patton et al 1988, Huston et al 1990). Since MFG are produced by an apocrine mechanism, each is surrounded by mammary apical cell membrane which encloses a large lipid droplet and a crescent of mammary epithelial cell cytosol. We believe that if we are able to understand the mechanisms responsible for milk production from a substrate, hormone and molecular basis that we might be in a better position to positively impact the numbers of women who can successfully breast feed their infants. PRELIMINARY STUDIES/PROGRESS REPORT We have recently demonstrated that we can isolate and quantitate by RT-PCR a number of mRNA species from the milk fat globule in human milk, including a-lactalbumen which is thought to be a key co-factor increasing the activity of galactosyl transferase, a key enzyme in the production of lactose (Stacey et al 1995). The development of this technique we hope will permit us the opportunity to study in vivo regulation of hormonal regulation of transcription and translation of a number of potentially regularoty proteins in the mammary epithelial cell of the human breast. Nipple stimulation as a result of infant suckling or the use of a breast pump triggers a nipple-pituitary reflex resulting in the secretion of both oxytocin and prolactin (Cos 1996). From our initial studies we observed a significant variation of a-lactalbumin mRNA in the milk samples that we have obtained but that this concentration clearly increase over the first 2-3 days of rhGH administration (unpublished data). We believe that these variations may reflect the fact that we were not sensitive to the potential impace of the timing of the obtaining of milk samples in relationship to the last breast feeding.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 假设 假设：H1：通过乳腺泵完全清空乳房诱导的催乳素和催产素的生理增加，而不是频繁的小乳房乳房排空的mRNA会增加α-乳al的mRNA。 具体目的： 该方案将试图确定收集时间与乳房相关的时间是否会影响牛奶脂肪球（MFG）中的mRNA含量，并确定该mRNA浓度的变化以及催生和催产素的血浆浓度的变化关系。 背景和意义： 母乳是母乳的理想食物，用于母乳喂养的婴儿和婴儿的胃炎，中耳炎和许多过敏性疾病（母乳喂养工作组）的发病率较低。 美国儿科学会建议婴儿在生命的前6个蒙多德（Mondhs）喂母乳，并部分喂母乳，最多为1年（美国儿科政策学院）。 许多妇女在母乳喂养方面挣扎，尝试成功的女性不到25％超过1个月。 假定乳糖的产生是人乳的主要调节剂，因为它是牛奶中的主要渗透剂（Mephan 1987）。 与牛奶蛋白和脂肪相反，牛奶水中的乳糖浓度是从母乳喂养的开始到末期的恒定，但是特定于物种的（Davies等，1983）。 Over the past several years, we have demonstrated using stable isotope tracers of glucose that 50 to 60% of lactose is derived from maternal plasma glucose but that up to 40 to 50% of lactose in human milk is derived from a process of de novo synthesis of lactose within the mammary epithelium (Sunehag et al 2002, Sunehag et al 2003). 尽管RHGH增加了30％的牛奶产量增加了30％，但源自十六种生成的乳糖的比例受禁食的影响，但不受RHGH治疗的影响（Kaplan等人）。 在人类中，无法控制六氧杆菌生成和乳糖合成的机制。 人牛奶中的脂肪成分似乎是牛奶脂肪球（MFG）（Patton等，1988，Huston等，1990）。 由于MFG是由占地机制产生的，因此每种机制都被乳腺顶端膜包围，该乳细胞膜包围了大脂质液滴和乳腺上皮细胞胞质醇的新月。 我们认为，如果我们能够理解负责从底物，激素和分子基础产生牛奶生产的机制，那么我们可能会更好地影响可以成功地影响能够成功母乳喂养婴儿的女性人数。 初步研究/进度报告 我们最近证明，我们可以通过RT-PCR分离和定量人类牛奶中的牛奶脂肪球，包括A-乳脂蛋白，这被认为是关键的co因子，从而增加了半乳糖基转移酶的活性，乙酰乳糖基转移酶的活性，这是乳糖产生的关键酶（Stacey等人，1995年）。 我们希望这项技术的开发能够使我们有机会研究人乳房乳腺上皮细胞中许多潜在的常规蛋白的转录和翻译的体内调节。 乳头刺激是由于婴儿哺乳或使用吸奶器触发乳头 - 垂体反射，从而导致催产素和催乳素分泌（COS 1996）。 从我们的最初研究中，我们观察到我们获得的牛奶样品中A-乳蛋白mRNA的显着变化，但是在RHGH给药的前2-3天内，这种浓度明显增加（未发表的数据）。 我们认为，这些变化可能反映出这样一个事实，即我们对获得牛奶样品与上次母乳喂养有关的时机的潜在爆发不敏感。