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.

项目摘要 这项建议的总体目标是调查产前雄激素与 从生命过程的角度看成人心脏代谢结果。越来越多的证据 表明产前暴露于雄激素可能在代谢的编程中发挥作用， 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了几种心脏代谢 成年后的高血压、胰岛素抵抗和肥胖症等疾病。孕妇 多囊卵巢综合征（PCOS）患者在怀孕期间的睾酮水平较高， 分娩与健康母亲相比，其后代往往发展更差的代谢 参数尽管动物研究和患者特定人群（即，PCOS），数据 在一般人群中，将产前雄激素与成人健康结果联系起来， 好好研究。发育雄激素化的问题是临床相关的调查 由于人类越来越多地暴露于内分泌干扰的环境因素， 雄激素受体信号传导。我们提出了一项研究，其中：1）我们将涉及产妇产前 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）测试他们的 对预测45年后成人心脏代谢风险的影响。此外，拟议的研究 促进我们对雄激素对心血管疾病的早期编程作用的理解， 标记物，可以帮助识别人类疾病的生物标志物，潜在的治疗靶点和早期 干预期。

项目成果

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

• DOI: 10.1016/j.mce.2017.07.010
• 发表时间: 2018-03-15
• 期刊: MOLECULAR AND CELLULAR ENDOCRINOLOGY
• 影响因子: 4.1
• 作者: Huang, Grace;Basaria, Shehzad
• 通讯作者: Basaria, Shehzad

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”。

• DOI: 10.1210/jc.2018-02015
• 发表时间: 2019
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Huang,Grace;Basaria,Shehzad;Bhasin,Shalender;Harman,SMitchell;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。

• DOI: 10.1089/jwh.2020.8467
• 发表时间: 2021
• 期刊: Journal of women's health (2002)
• 作者: Holsen,LauraM;Huang,Grace;Cherkerzian,Sara;Aroner,Sarah;Loucks,EricB;Buka,Steve;Handa,RobertJ;Goldstein,JillM
• 通讯作者: Goldstein,JillM