Urinary peptide excretion and onset of puberty

尿肽排泄和青春期开始

基本信息

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
项目类别：
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

项目摘要

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）：该项目的短期目标是利用蛋白质组学方法来定义青春期发作的时间和阶段。该研究将利用NCI资助的U54观察性研究中从10-13岁的女孩中收集的尿液和血液样本。在研究入口和接下来的12个月和24个月时，从年龄段的女孩那里获得标本。饮食问卷是在每个时间点进行的。进行每月问卷和电话采访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期间发生的生化和生理事件，因为一项对遗传相同双胞胎的研究强烈建议，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，青春期的发作早期，成人患乳腺癌的风险越高。假设是，青春期会导致类固醇敏感基因表达的明显变化，从而导致其产物，即蛋白质。由于大多数细胞寿命相对较短（日周），因此中的蛋白质会受到失误，并以血液作为肽出现。此外，由于青春期期间人体的大规模重新分布，非雌激素敏感组织中蛋白质的肽也会发生显着变化。尽管尿液含有一些完整的蛋白质，但肾肾小球过滤导致大部分可检测的肽低于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得出，并最终开发了纳米型MRM倾斜MS方法，以定量测定青春期相关的肽。（2）使用既定程序，以评估年龄，时间或以来的初潮和种族/民族的影响；使用纵向收集的标本对这些标记进行验证，这些标本对经历青春期的个别女孩的标本，考虑到年龄，时间或初级或自初级成年或种族/民族的任何差异；（3）确定高大豆饮食是否会影响使用这些肽标志物测量的青春期发育，考虑到这些因素的任何混杂，并确定这些肽标志物的水平是否因年年大豆消耗水平是否有所不同。项目叙述：这项研究的目的是通过应用现代蛋白质组学方法来定义青春期发作阶段，以鉴定从一群高加索和亚洲女孩开始前后收集的尿液中收集的尿液中的肽。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变化。还将检查大豆异黄酮的饮食摄入量和种族/种族对肽标志物的影响。