Prenatal Androgens and Cardiometabolic Risk in Adulthood

产前雄激素和成年后的心脏代谢风险

• 批准号: 9898427
• 负责人: Grace Huang
• 金额: $ 12.91万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-15 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898427
• 关键词: 7 year old; Adult; Adult Children; Adverse effects; Age; Age-Years; Androgen Receptor; Androgenization; Androgens; Animal Model; Animals; Biological Assay; Biological Markers; Birth; Blood Pressure; Boston; Cardiovascular Diseases; Cardiovascular system; Central obesity; Childhood; Clinical; Communities; Data; Development; Dyslipidemias; Endocrine disruption; Environmental Risk Factor; Exposure to; Family Study; Female; Fetal Growth; Fetal Growth Retardation; Genetic Risk; Goals; Growth; Health; Human; Hypertension; Impairment; Individual; Insulin Resistance; Intervention; Investigation; Life; Life Cycle Stages; Link; Lipids; Liquid Chromatography; Low Birth Weight Infant; Massachusetts; Measures; Mediating; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolic syndrome; Mothers; New England; Obesity; Outcome; Participant; Pathway interactions; Patients; Perinatal; Play; Polycystic Ovary Syndrome; Population; Pregnancy; Pregnant Women; Receptor Signaling; Resources; Rhode Island; Risk Factors; Role; Serum; Sex Differences; Site; Source; Surrogate Markers; Testing; Testosterone; Third Pregnancy Trimester; Variant; adult obesity; base; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; cardiovascular risk factor; clinically relevant; cohort; critical developmental period; early childhood; exposed human population; fasting glucose; fetal; fetal programming; follow-up; genetic association; glucose metabolism; human disease; in utero; interest; male; maternal serum; mortality; novel; obesity in children; offspring; postnatal; pregnant; prenatal; prenatal exposure; primary outcome; public health relevance; recruit; sex; tandem mass spectrometry; therapeutic target; trait

Project Summary The overall goal of this proposal is to investigate the relationship between prenatal androgens and adult cardiometabolic outcomes in a human cohort taking a life-course perspective. Growing evidence suggests that prenatal exposure to androgens may play a role in the programming of metabolic dysfunction and cardiovascular disease in adulthood. Evidence from prenatally androgenized animal models exposed to testosterone in early and late gestation demonstrate several cardiometabolic impairments including hypertension, insulin resistance and adiposity in adult life. Pregnant women with polycystic ovary syndrome (PCOS) have higher testosterone levels during pregnancy and delivery compared to healthy mothers and their offspring tend to develop worse metabolic parameters. Despite evidence from animal studies and patient-specific populations (ie. PCOS), data linking prenatal androgens to adult health outcomes in the general human population has not been well studied. The issue of developmental androgenization is of clinical relevance for investigation because of increasing human exposure to endocrine-disrupting environmental factors that interact with androgen receptor signaling. We propose a study in which: 1) we will relate maternal prenatal androgen levels to offspring early childhood indicators of growth (from birth to age 7), and 2) test their impact on predicting cardiometabolic risk in adulthood 45 years later. The proposed study, in addition to advancing our understanding of early programming effects of androgens on cardiovascular markers, can help identify biomarkers for human disease, potential therapeutic targets and early periods for intervention.

项目概要 该提案的总体目标是调查产前雄激素与产前雄激素之间的关系。 从生命历程的角度来看，人类队列中的成人心脏代谢结果。越来越多的证据 表明产前接触雄激素可能在代谢编程中发挥作用 成年后的功能障碍和心血管疾病。来自产前雄激素化动物的证据 在妊娠早期和晚期暴露于睾酮的模型显示出多种心脏代谢 成人生活中的损害包括高血压、胰岛素抵抗和肥胖。孕妇 多囊卵巢综合症 (PCOS) 患者在怀孕期间睾酮水平较高，并且 与健康的母亲相比，分娩的母亲及其后代的新陈代谢往往更差 参数。尽管有来自动物研究和患者特定人群（即 PCOS）的证据，但数据 尚未将产前雄激素与一般人群的成年健康结果联系起来 好好研究了。发育性雄激素化问题与研究具有临床相关性 因为人类越来越多地暴露于相互作用的内分泌干扰环境因素中 与雄激素受体信号传导。我们提出一项研究：1）我们将把母亲产前 雄激素水平对后代早期儿童生长指标（从出生到 7 岁）的影响，以及 2) 测试其 对预测 45 年后成年期心脏代谢风险的影响。此外，拟议的研究 增进我们对雄激素对心血管的早期编程影响的理解 标记物，可以帮助识别人类疾病的生物标记物、潜在的治疗靶点和早期治疗 干预期。

项目成果

Do anabolic-androgenic steroids have performance-enhancing effects in female athletes?

合成代谢雄激素类固醇对女运动员有提高成绩的作用吗？

• 发表时间: 2018-03-15
• 影响因子: 4.1
• 作者: Huang, Grace;Basaria, Shehzad
• 通讯作者: Basaria, Shehzad

Effect of Protein Intake on Lean Body Mass in Functionally Limited Older Men: A Randomized Clinical Trial.

蛋白质摄入量对功能受限的老年男性去脂体重的影响：一项随机临床试验。

• 发表时间: 2018-04-01
• 影响因子: 39
• 作者: Bhasin, Shalender;Apovian, Caroline M;Travison, Thomas G;Pencina, Karol;Moore, Lynn L;Huang, Grace;Campbell, Wayne W;Li, Zhuoying;Howland, Andrew S;Chen, Ruo;Knapp, Philip E;Singer, Martha R;Shah, Mitali;Secinaro, Kristina;Eder, Richard V;H
• 通讯作者: H

Response to Letter to the Editor: "Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With Low or Low-Normal Testosterone Levels".

回复给编辑的信：“长期睾酮管理对睾酮水平低或正常低的老年男性胰岛素敏感性的影响”。

• 发表时间: 2019
• 作者: Huang, Grace;Basaria, Shehzad;Bhasin, Shalender;Harman, S Mitchell;Tsitouras, Panayiotis
• 通讯作者: Tsitouras, Panayiotis

Sex Differences in Hemoglobin A1c Levels Related to the Comorbidity of Obesity and Depression.

糖化血红蛋白水平的性别差异与肥胖和抑郁症的共病相关。

• 发表时间: 2021
• 作者: Holsen, Laura M;Huang, Grace;Cherkerzian, Sara;Aroner, Sarah;Loucks, Eric B;Buka, Steve;Handa, Robert J;Goldstein, Jill M
• 通讯作者: Goldstein, Jill M