Developmental programming: influence of sex steroids and mechanisms

发育规划:性类固醇的影响和机制

基本信息

项目摘要

PROJECT SUMMARY Adverse intrauterine environment during the critical period of fetal development predisposes organisms to increased risk for developing hypertension. We and others using a low-protein (LP) model of fetal programming demonstrated that hypertension in offspring is gender related, with a greater effect in males than females, and endocrine changes may underlie the development of hypertension. The central hypothesis is that sex steroid hormones, testosterone (T) and estradiol (E2), via interaction with a variety of regulatory path- ways, regulate the development and progression of maternal LP-induced hypertension in the offspring. Effects include changes in vascular steroid receptors, endothelial and smooth muscle (VSM) function, and vascular rennin angiotensin system (RAS). Three specific aims are proposed. Specific Aim 1: Investigate the influence of sex steroids on maternal LP-induced developmental origins of hypertension in male and female offspring. Specific Aim 1a. Is the onset and severity of hypertension related to changes in sex steroids? We hypothesize that endocrine dysfunction will precede the development of hypertension with a more pronounced effect in males than females. Specific Aim 1b. Are alterations in blood pressure (BP) in the offspring specific to changes in the levels of sex steroids? We hypothesize that OVX in females exacerbates, while OCX in males dampens, the onset and severity of hypertension, and these changes are reversed by respective steroid replacement and flutamide. Growth rate, adiposity, and changes in MAP and plasma T and E2 will be assessed. Specific Aim 2: Characterization of endothelial and VSM cell functions and their regulation by sex steroids in hypertensive offspring. We hypothesize that endocrine dysfunction will alter expression of steroid receptors, endothelial, and VSM functions in LP offspring, and these effects are hormone specific. Specific Aim 2a. Are alterations in BP in the offspring specific to changes in the levels of sex steroid receptors? Specific Aim 2b. Is endothelial cell function altered and related to changes in T and E2 levels in hypertensive offspring? Specific Aim 2c. Is VSM cell function altered and related to changes in T and E2 levels in hypertensive offspring? Specific Aim 2d. Are alterations in the function of endothelium and VSM specific to changes in T and E2 levels in hypertensive offspring? Specific Aim 3: Characterization of vascular RAS function and regulation by sex steroids in hypertensive offspring. We hypothesize that alteration in T and E2 levels will alter expression and activity of RAS components, and thus BP, in LP offspring. Specific Aim 3a. Is the function and expression of RAS components altered with age and related to changes in T and E2 levels in the hypertensive offspring? Specific Aim 3b. Are the expression and activity of RAS components in hyper- tensive offspring specific to changes in T and E2 using gonadectomy in LP offspring? The study will assess if these changes are reversed with respective hormones and flutamide. Collectively, these studies will yield important insights that could aid in developing sex-specific strategies for preventing and treating hypertension.
项目总结 胎儿发育关键期不利的宫内环境易使生物体 患高血压的风险增加。我们和其他人使用低蛋白(LP)的胎儿编程模型 证明后代的高血压与性别有关,男性的影响比女性更大,以及 内分泌变化可能是高血压发生的基础。中心假设是性行为 类固醇激素,睾酮(T)和雌二醇(E2),通过与多种调节途径相互作用- 调控母系脂蛋白所致子代高血压的发生发展。 影响包括血管类固醇受体、内皮和平滑肌(VSM)功能的变化, 血管肾素血管紧张素系统(RAS)。提出了三个具体目标。具体目标1: 性激素对低密度脂蛋白诱导的男性高血压母系发育的影响 以及雌性后代。具体目标1a。高血压的发病和严重程度是否与性别变化有关? 类固醇?我们假设内分泌功能障碍会先于高血压的发展。 对男性的影响比对女性更明显。具体目标1b。是血压(BP)的改变 后代对性激素水平的变化有特异性吗?我们假设女性体内的OVX会加剧, 虽然男性的OCX抑制了高血压的发病和严重程度,但这些变化被以下因素逆转 分别使用类固醇替代药物和氟他胺。生长速度、肥胖度以及MAP和血浆T和 将对E2进行评估。具体目标2:内皮细胞和血管内皮细胞功能的特征及其 性类固醇对高血压后代的调节作用。我们假设内分泌功能障碍会改变 类固醇受体、内皮细胞和VSM功能在LP后代中的表达,这些影响是激素 具体的。具体目标2a。子代的血压变化是否与性激素水平的变化有关 受体?具体目标2b。血管内皮细胞功能是否改变并与T和E_2水平的变化有关 高血压后代?具体目标2c。VSM细胞功能是否改变并与T和E2水平的变化有关 在高血压后代身上?具体目标2d。血管内皮细胞功能的改变和VSM是否特定于 高血压子代T和E_2水平的变化?具体目标3:血管RAS的特征 性激素对高血压子代的作用和调节。我们假设T和E_2的变化 在LP后代中,水平会改变RAS组分的表达和活性,从而改变BP。具体目标3a。是 Ras组分的功能和表达随年龄的变化及其与T和E_2水平变化的关系 高血压后代?具体目标3b。RAS组分在超微结构中的表达和活性 在LP子代中,性腺切除对T和E_2的变化有特异性的紧张子代吗?该研究将评估是否 这些变化被各自的激素和氟他胺逆转。总而言之,这些研究将产生 有助于制定针对性别的高血压预防和治疗策略的重要见解。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

CHANDRASEKHAR YALLAMPALLI其他文献

CHANDRASEKHAR YALLAMPALLI的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('CHANDRASEKHAR YALLAMPALLI', 18)}}的其他基金

Developmental programming: influence of sex steroids and mechanisms
发育规划:性类固醇的影响和机制
  • 批准号:
    8751210
  • 财政年份:
    2010
  • 资助金额:
    $ 36.41万
  • 项目类别:
Developmental programming: influence of sex steroids and mechanisms
发育规划:性类固醇的影响和机制
  • 批准号:
    8197579
  • 财政年份:
    2010
  • 资助金额:
    $ 36.41万
  • 项目类别:
Developmental programming: influence of sex steroids and mechanisms
发育规划:性类固醇的影响和机制
  • 批准号:
    8056426
  • 财政年份:
    2010
  • 资助金额:
    $ 36.41万
  • 项目类别:
Nitric oxide regulation of CD55 and infection
一氧化氮对 CD55 和感染的调节
  • 批准号:
    8206846
  • 财政年份:
    2009
  • 资助金额:
    $ 36.41万
  • 项目类别:
Nitric oxide regulation of CD55 and infection
一氧化氮对 CD55 和感染的调节
  • 批准号:
    8403523
  • 财政年份:
    2009
  • 资助金额:
    $ 36.41万
  • 项目类别:
Nitric oxide regulation of CD55 and infection
一氧化氮对 CD55 和感染的调节
  • 批准号:
    8794626
  • 财政年份:
    2009
  • 资助金额:
    $ 36.41万
  • 项目类别:
Nitric oxide regulation of CD55 and infection
一氧化氮对 CD55 和感染的调节
  • 批准号:
    8004069
  • 财政年份:
    2009
  • 资助金额:
    $ 36.41万
  • 项目类别:
Nitric oxide regulation of CD55 and infection
一氧化氮对 CD55 和感染的调节
  • 批准号:
    7759623
  • 财政年份:
    2009
  • 资助金额:
    $ 36.41万
  • 项目类别:
Low birth weight, uterine infection, and nitric oxide
低出生体重、子宫感染和一氧化氮
  • 批准号:
    6695283
  • 财政年份:
    2002
  • 资助金额:
    $ 36.41万
  • 项目类别:
Low birth weight, uterine infection, and nitric oxide
低出生体重、子宫感染和一氧化氮
  • 批准号:
    7151219
  • 财政年份:
    2002
  • 资助金额:
    $ 36.41万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
  • 批准号:
    2230829
  • 财政年份:
    2023
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 36.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了