STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
类固醇激素的合成/失活及其在肺发育末期的作用
基本信息
- 批准号:RGPIN-2016-05870
- 负责人:
- 金额:$ 2.04万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2016
- 资助国家:加拿大
- 起止时间:2016-01-01 至 2017-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The goal of this study is to characterize the role of androgens in the development of 3D lung structure. Androgens are known as male sex steroids but they exist in the blood of both sexes, although at higher levels for males. We showed in a recent experiment that when the effect of androgens is blocked by administration of a pure antiandrogen (flutamide) to neonatal mice, the last step of lung development (alveolarization) is altered and an obvious defect in lung structure is observed. Surprisingly, our data indicate that flutamide had the same effect in both sexes, showing that androgens are essential for normal lung development of males and females. We know that several genes expressed in the developing lung encode for enzymes showing the capability to synthesize active androgens from an inactive molecule, while other genes produce enzymes able to inactivate androgens. Our hypothesis in this grant is that site-specific expression of the genes involved in androgen synthesis and inactivation results in a multitude of microenvironments with site-specific levels of androgens, which control the development of the 3D structure of the lung. This concept indicates that growth of the lung along each axis (x,y,z) is a tightly orchestrated process. During the next 5 years, I propose to study the involvement of the androgen activating and inactivating genes in lung development: 1) by studying their levels of expression over time during lung development; 2) by characterizing their exact site of expression in the developing lung at different developmental times, and; 3) by examining the lung structure after administration of gene-specific inhibitors (siRNA). This study will be performed in both sexes. The potential of androgens to modulate 3D-lung development makes this fundamental research program very useful for all researchers working on organogenesis and tissue engineering.
本研究的目的是描述雄激素在3D肺结构发育中的作用。雄激素被称为男性性类固醇,但它们存在于两性的血液中,尽管男性的水平较高。我们在最近的一项实验中表明,当雄性激素的作用被一种纯抗雄激素(氟替卡松)给药新生小鼠阻断时,肺发育的最后一步(肺泡化)被改变,观察到肺结构的明显缺陷。令人惊讶的是,我们的数据表明,氟替卡松在两种性别中具有相同的效果,表明雄激素对男性和女性的正常肺发育至关重要。我们知道,在发育中的肺中表达的几种基因编码的酶显示出从非活性分子合成活性雄激素的能力,而其他基因产生的酶能够使雄激素活化。我们在这项研究中的假设是,参与雄激素合成和失活的基因的位点特异性表达导致大量具有位点特异性水平的雄激素的微环境,其控制肺的3D结构的发育。该概念表明肺沿着每个轴(x,y,z)的生长是紧密协调的过程。在接下来的5年里,我建议研究雄激素激活和失活基因在肺发育中的参与:1)通过研究它们在肺发育过程中随时间的表达水平; 2)通过表征它们在不同发育时间在发育中的肺中的确切表达位点; 3)通过检查基因特异性抑制剂(siRNA)给药后的肺结构。本研究将在两种性别中进行。雄激素调节3D肺发育的潜力使这个基础研究项目对所有从事器官发生和组织工程的研究人员非常有用。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Tremblay, Yves其他文献
Automated High-Performance Analysis of Lung Morphometry
- DOI:
10.1165/rcmb.2014-0469ma - 发表时间:
2015-08-01 - 期刊:
- 影响因子:6.4
- 作者:
Sallon, Celine;Soulet, Denis;Tremblay, Yves - 通讯作者:
Tremblay, Yves
Levels of Dihydrotestosterone, Testosterone, Androstenedione, and Estradiol in Canalicular, Saccular, and Alveolar Mouse Lungs
- DOI:
10.1007/s00408-010-9231-x - 发表时间:
2010-06-01 - 期刊:
- 影响因子:5
- 作者:
Boucher, Eric;Provost, Pierre R.;Tremblay, Yves - 通讯作者:
Tremblay, Yves
Essential Intracrine Androgenic Action in Lung Development for Both Sexes
- DOI:
10.1016/j.jsbmb.2018.06.012 - 发表时间:
2018-10-01 - 期刊:
- 影响因子:4.1
- 作者:
Sallon, Celine;Provost, Pierre R.;Tremblay, Yves - 通讯作者:
Tremblay, Yves
Ovine model of congenital chest wall and spine deformity: From birth to 3 months follow-up.
- DOI:
10.1002/jsp2.1295 - 发表时间:
2024-03 - 期刊:
- 影响因子:3.7
- 作者:
Shen, Jesse;Samson, Nathalie;Lamontagne-Proulx, Jerome;Soulet, Denis;Tremblay, Yves;Bazin, Marc;Nadeau, Charlene;Bouchard, Sarah;Praud, Jean-Paul;Parent, Stefan - 通讯作者:
Parent, Stefan
Elevated expression of four apolipoprotein genes during the 32-35 week gestation window in the human developing lung
- DOI:
10.1016/j.earlhumdev.2010.06.013 - 发表时间:
2010-09-01 - 期刊:
- 影响因子:2.5
- 作者:
Provost, Pierre R.;Tremblay, Yves - 通讯作者:
Tremblay, Yves
Tremblay, Yves的其他文献
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{{ truncateString('Tremblay, Yves', 18)}}的其他基金
STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
类固醇激素的合成/失活及其在肺发育末期的作用
- 批准号:
RGPIN-2016-05870 - 财政年份:2021
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
类固醇激素的合成/失活及其在肺发育末期的作用
- 批准号:
RGPIN-2016-05870 - 财政年份:2020
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
类固醇激素的合成/失活及其在肺发育末期的作用
- 批准号:
RGPIN-2016-05870 - 财政年份:2019
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
类固醇激素的合成/失活及其在肺发育末期的作用
- 批准号:
RGPIN-2016-05870 - 财政年份:2018
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
类固醇激素的合成/失活及其在肺发育末期的作用
- 批准号:
RGPIN-2016-05870 - 财政年份:2017
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Steroid hormone synthesis/inactivation and action in terminal lung development
类固醇激素合成/失活及其在肺终末发育中的作用
- 批准号:
171140-2010 - 财政年份:2014
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Steroid hormone synthesis/inactivation and action in terminal lung development
类固醇激素合成/失活及其在肺终末发育中的作用
- 批准号:
171140-2010 - 财政年份:2013
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Steroid hormone synthesis/inactivation and action in terminal lung development
类固醇激素合成/失活及其在肺终末发育中的作用
- 批准号:
171140-2010 - 财政年份:2012
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
ChemiDoc MP Imaging System
ChemiDoc MP 成像系统
- 批准号:
440371-2013 - 财政年份:2012
- 资助金额:
$ 2.04万 - 项目类别:
Research Tools and Instruments - Category 1 (<$150,000)
Steroid hormone synthesis/inactivation and action in terminal lung development
类固醇激素合成/失活及其在肺终末发育中的作用
- 批准号:
171140-2010 - 财政年份:2011
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
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STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
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类固醇激素的合成/失活及其在肺发育末期的作用
- 批准号:
RGPIN-2016-05870 - 财政年份:2019
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
类固醇激素的合成/失活及其在肺发育末期的作用
- 批准号:
RGPIN-2016-05870 - 财政年份:2018
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
STEROID HORMONE SYNTHESIS/INACTIVATION AND ACTION IN TERMINAL LUNG DEVELOPMENT
类固醇激素的合成/失活及其在肺发育末期的作用
- 批准号:
RGPIN-2016-05870 - 财政年份:2017
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Steroid hormone synthesis/inactivation and action in terminal lung development
类固醇激素合成/失活及其在肺终末发育中的作用
- 批准号:
171140-2010 - 财政年份:2014
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Steroid hormone synthesis/inactivation and action in terminal lung development
类固醇激素合成/失活及其在肺终末发育中的作用
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