Urinary peptide excretion and onset of puberty

尿肽排泄和青春期开始

• 批准号: 7846995
• 负责人: STEPHEN BARNES
• 金额: $ 13.34万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7846995
• 关键词: 13 year old; 7 year old; Accounting; Address; Adult; Age; Age at Menarche; Aging; Anabolism; Area; Asians; Axilla; Biochemical; Biological Assay; Blood; Blood specimen; Breast; California; Caucasians; Caucasoid Race; Cells; Characteristics; Cohort Studies; Consumption; Data; Development; Diet; Dietary Questionnaires; Dietary intake; Endocrine; Entire hair of pubis; Estrogens; Ethnic Origin; Event; Excretory function; Filtration; Funding; Genes; Genetic; Goals; Gonadotropins; Growth; Hair; High Pressure Liquid Chromatography; Hip region structure; Hypothalamic structure; Hypoxia Inducible Factor; Individual; Ions; Isoflavones; Kidney Glomerulus; Lasers; Leg; Life; Longitudinal Studies; Luteinizing Hormone; MALDI-TOF Mass Spectrometry; Measures; Menarche; Menstruation; Methods; Molecular Weight; Monitor; Monozygotic twins; Nutrient; Observational Study; Peptide Fragments; Peptides; Physiological; Pituitary Gland; Procedures; Proteins; Proteomics; Puberty; Questionnaires; Race; Reaction; Recruitment Activity; Research Personnel; Risk; Series; Signal Transduction; Specimen; Specimen Handling; Spottings; Staging; Steroids; Techniques; Telephone Interviews; Time; Tissues; Twin Studies; Urine; Width; age difference; age related; cancer risk; cohort; early onset; epidemiologic data; gene interaction; girls; malignant breast neoplasm; nano; racial and ethnic; response; soy; soy protein isolate; urinary

DESCRIPTION (provided by applicant): The short-term goal of this project is to utilize a proteomics approach to define the timing and stages of the onset of puberty. The study will utilize urine and blood samples collected previously from girls between the ages of 10-13 in an NCI-funded U54 observational study. Specimens were obtained from pre-menarcheal girls at study entry and at the following 12 and 24 months. Dietary questionnaires were taken at each time-point. Monthly questionnaires and telephone interviews were performed to assess the development of puberty. The long-term goal of this study is to better understand the biochemical and physiological events that occur during puberty since a study in genetically identical twins strongly suggested that the onset of puberty was controlled by external environmental effects, not genetic factors. In addition, the study found that earlier the onset of puberty, the higher the adult risk of breast cancer. The hypothesis is that puberty causes marked changes in the expression of steroid-sensitive genes and hence their products, the proteins. Since most cell lifetimes are relatively short (days-weeks), the proteins in them are subjected to turnover and will appear in blood as peptides. In addition, because of the large-scale redistribution of the body during puberty, peptides from proteins in non-estrogen sensitive tissues will also undergo significant changes. Although urine contains some intact proteins, filtration by kidney glomeruli results in the bulk of detectable peptides being below 20 kDa. The peptides will be recovered from urine using a high throughput hydrophobic cartridge and then eluted to yield a predominantly peptide fractionIn this study, we will (1) first use MALDI-TOF MS to establish potential peptides which statistically differ between pre-menarcheal and post-menarcheal Caucasian girls consuming a low soy diet, then use nanoLC-MALDI and tandem MS to identify the proteins from which the peptides were derived, and finally develop nanoLC-MRM-tandem MS methods to quantitatively assay the puberty-associated peptides; (2) using the established procedure, to evaluate whether age, time to or since menarche, and race/ethnicity impact these markers; to validate these markers using longitudinally collected specimens on individual girls going through puberty, taking into account any differences by age, time to or since menarche, or race/ethnicity identified in this aim; and (3) to determine if a high soy diet impacts pubertal development, as measured using these peptide markers, taking into account any confounding by the factors, and to determine if the levels of these peptide markers differ by level of soy consumption in pre-menarcheal and post-menarcheal girls. Project Narrative: The goal of this study is to define the stages of onset of puberty by applying modern proteomics methods to identify peptides in urines collected before and after the onset of menarche from a cohort of Caucasian and Asian girls. Longitudinal studies will allow the investigators to distinguish age-related change changes that are distinct from puberty itself. The effects of dietary intake of soy isoflavones and of race/ethnicity on the peptide markers will also be examined.

描述（由申请人提供）： 这个项目的短期目标是利用蛋白质组学方法来确定青春期开始的时间和阶段。该研究将利用先前在NCI资助的U 54观察性研究中从10-13岁女孩中收集的尿液和血液样本。在研究入组时以及随后的12个月和24个月，从月经初潮前女孩中获得标本。在每个时间点进行饮食问卷调查。每月进行问卷调查和电话访谈，以评估青春期的发展。这项研究的长期目标是更好地了解青春期发生的生化和生理事件，因为一项对基因相同的双胞胎的研究强烈表明，青春期的开始是由外部环境影响控制的，而不是遗传因素。此外，研究发现，青春期开始越早，成年后患乳腺癌的风险越高。这一假说认为，青春期引起类固醇敏感基因表达的显著变化，从而引起其产物蛋白质的显著变化。由于大多数细胞的寿命相对较短（数天-数周），因此它们中的蛋白质会发生周转，并以肽的形式出现在血液中。此外，由于青春期机体会发生大规模的再分配，来自非雌激素敏感组织中蛋白质的肽也会发生明显的变化。虽然尿液中含有一些完整的蛋白质，但肾小球的过滤导致可检测到的肽的体积低于20 kDa。在本研究中，我们将（1）首先使用MALDI-TOF MS来确定在月经前期和月经后期进食低大豆饮食的高加索女孩之间统计学上不同的潜在肽，然后使用nanoLC-MALDI和串联MS来鉴定肽来源的蛋白质，（2）使用已建立的程序，评估年龄、月经初潮时间或自月经初潮以来的时间以及种族/民族是否影响这些标志物;使用纵向收集的青春期女孩个体样本验证这些标志物，考虑到年龄、初潮时间或初潮后的任何差异，或在此目的中鉴定的种族/民族;和（3）确定高大豆饮食是否影响青春期发育，如使用这些肽标志物测量的，考虑到由这些因素引起的任何混淆，并确定这些肽标志物的水平是否因月经初潮前和月经初潮后女孩的大豆消耗水平而不同。 项目叙述：本研究的目的是通过应用现代蛋白质组学方法来确定青春期开始的阶段，以确定从一个队列的白人和亚洲女孩的月经初潮开始之前和之后收集的尿液中的肽。纵向研究将使研究人员能够区分与青春期本身不同的年龄相关的变化。还将检查大豆异黄酮饮食摄入量和种族/民族对肽标志物的影响。