Reversible vitamin A-dependent arrest of spermatogonia
可逆的维生素 A 依赖性精原细胞停滞
基本信息
- 批准号:6680614
- 负责人:
- 金额:$ 23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-07-07 至 2008-04-30
- 项目状态:已结题
- 来源:
- 关键词:DNA binding protein RNase protection assay Sertoli cells activins biological signal transduction cell growth regulation cell proliferation contraceptives cyclin dependent kinase enzyme inhibitors follistatin genetic transcription hormone receptor inhibin laboratory rat northern blottings nucleic acid purification paracrine protein biosynthesis retinoids sperm testis vitamin A deficiency
项目摘要
DESCRIPTION (provided by applicant): The broad, long-range objective of this project is the rational design of contraceptive strategies based on the reversible arrest of spermatogonia (Spg) in the vitamin A-deficient (VAD) testis. Our intent is to uncover specific mechanisms that reversibly arrest Spg in this model. Of the two pertinent cell types (arrested Spg and Sertoli cells) in the epithelium of the VAD testis, only the Sertoli cell expresses significant amounts of retinoic acid receptor-alpha (RARalpha). Thus, our overall hypothesis: paracrine signal(s) from Sertoli cells mediate the effects of vitamin A on Spg. Our working hypothesis is that Sertoli cell-derived activin arrests Spg in the VAD testis and that vitamin A rescues proliferation by down-regulating activin and up-regulating its binding protein follistatin-like protein. The objectives of this initial funding period are to identify future contraceptive targets by determining the role specific signaling molecules and pathways play during the vitamin A-dependent regulation of Spg proliferation. We intend to accomplish this by completing the following specific aims: (1) Test our prediction that vitamin A regulates specific signaling factors (activin, inhibin), binding proteins (follistatin, follistatin-related protein) and receptors (activin receptors i & ii). (2) Determine whether the vitamin a status of the testis regulates smad-dependent signaling pathways downstream of the activin receptor and synthesis of cyclin-dependent kinase inhibitor(s) to effect changes in the spermatogonial cell cycle. (3) Test the efficacy of candidate factors to regulate the proliferation of Spg and test our hypothesis that activin-dependent signaling regulates cyclin-dependent kinase inhibitors to effect these changes. (4) Identify additional paracrine factors and receptors that participate in the reversible VAD arrest of spermatogonia. Completing these aims will define specific mechanisms that reverse an intrinsic checkpoint in the genetic program directing spermatogonial proliferation, a significant advance towards our goal of designing a successful male contraceptive.
描述(由申请人提供):该项目的广泛、长期目标是基于维生素 A 缺乏 (VAD) 睾丸中精原细胞 (Spg) 的可逆抑制来合理设计避孕策略。我们的目的是揭示在此模型中可逆地阻止 Spg 的具体机制。在 VAD 睾丸上皮细胞的两种相关细胞类型(停滞的 Spg 和支持细胞)中,只有支持细胞表达大量的视黄酸受体-α (RARα)。因此,我们的总体假设是:来自支持细胞的旁分泌信号介导维生素 A 对 Spg 的影响。我们的工作假设是,支持细胞来源的激活素可阻止 VAD 睾丸中的 Spg,而维生素 A 通过下调激活素和上调其结合蛋白卵泡抑素样蛋白来拯救增殖。该初始资助期的目标是通过确定特定信号分子和途径在维生素 A 依赖性 Spg 增殖调节过程中的作用来确定未来的避孕目标。我们打算通过完成以下具体目标来实现这一目标:(1)测试我们的预测,即维生素 A 调节特定信号因子(激活素、抑制素)、结合蛋白(卵泡抑素、卵泡抑素相关蛋白)和受体(激活素受体 i 和 ii) 。 (2) 确定睾丸的维生素a状态是否调节激活素受体下游的smad依赖性信号通路和细胞周期蛋白依赖性激酶抑制剂的合成,以影响精原细胞周期的变化。 (3)测试候选因子调节Spg增殖的功效,并测试我们的假设,即激活素依赖性信号传导调节细胞周期蛋白依赖性激酶抑制剂以影响这些变化。 (4) 确定参与精原细胞可逆 VAD 停滞的其他旁分泌因子和受体。完成这些目标将确定逆转指导精原细胞增殖的遗传程序中的内在检查点的具体机制,这对我们设计成功的男性避孕药的目标来说是一个重大进步。
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)
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JAMES K TSURUTA其他文献
JAMES K TSURUTA的其他文献
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{{ truncateString('JAMES K TSURUTA', 18)}}的其他基金
Increasing sensitivity and discrimination of breast cancer diagnosis using molecularly targeted, extravascular ultrasound imaging with ultrasound-activated, phase-change nanodroplet contrast agent
使用超声激活相变纳米液滴造影剂进行分子靶向血管外超声成像,提高乳腺癌诊断的灵敏度和辨别力
- 批准号:
9768466 - 财政年份:2018
- 资助金额:
$ 23万 - 项目类别:
Reversible vitamin A-dependent arrest of spermatogonia
可逆的维生素 A 依赖性精原细胞停滞
- 批准号:
6874405 - 财政年份:2003
- 资助金额:
$ 23万 - 项目类别:
Reversible vitamin A-dependent arrest of spermatogonia
可逆的维生素 A 依赖性精原细胞停滞
- 批准号:
6772495 - 财政年份:2003
- 资助金额:
$ 23万 - 项目类别:
Reversible vitamin A-dependent arrest of spermatogonia
可逆的维生素 A 依赖性精原细胞停滞
- 批准号:
7228881 - 财政年份:2003
- 资助金额:
$ 23万 - 项目类别:
Reversible vitamin A-dependent arrest of spermatogonia
可逆的维生素 A 依赖性精原细胞停滞
- 批准号:
7049394 - 财政年份:2003
- 资助金额:
$ 23万 - 项目类别:
相似海外基金
Reversible vitamin A-dependent arrest of spermatogonia
可逆的维生素 A 依赖性精原细胞停滞
- 批准号:
6874405 - 财政年份:2003
- 资助金额:
$ 23万 - 项目类别:
Reversible vitamin A-dependent arrest of spermatogonia
可逆的维生素 A 依赖性精原细胞停滞
- 批准号:
6772495 - 财政年份:2003
- 资助金额:
$ 23万 - 项目类别:
Reversible vitamin A-dependent arrest of spermatogonia
可逆的维生素 A 依赖性精原细胞停滞
- 批准号:
7049394 - 财政年份:2003
- 资助金额:
$ 23万 - 项目类别: