Androgenic Regulation of Epididymal Sperm Binding Proteins: Role of RNA-binding Proteins

附睾精子结合蛋白的雄激素调节：RNA 结合蛋白的作用

• 批准号: 9511822
• 负责人: Joe Hall
• 金额: $ 23.7万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-11-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9511822&HistoricalAwards=false
• 关键词: Androgenic; Regulation; Epididymal; Sperm; Binding

9511822 Hall In all male mammalian species, including man, spermatozoa that leave the testis are infertile and immobile. The acquisition of fertilizing capacity and motility by spermatozoa occurs in an organ called the epididymis and the overall process is often referred to as "sperm maturation". It is now well accepted in reproductive biology and biochemistry that spermatozoan maturation is mediated by proteins and glycoproteins called fertility antigens. These fertility antigens are secreted by the epididymis under the control of the male hormone, testosterone. Using the rat as an experimental model, Dr. Hall has identified a key fertility antigen that is secreted by the epididymis and binds to the sperm plasma membrane. This sperm plasma membrane antigen which is synthesized by the epididymis plays a key physiological role in plasma membrane changes on the surface spermatozoa that accompany the development of fertilizing capacity and motility in mammals. An initial step toward elucidating the basic causes of male infertility or developing compounds as potential male contraceptives is to understand how these fertility antigens are regulated in the mammalian epididymis. Thus, the broad, long-term objective of the present study is to provide a basic understanding of how fertility antigens are regulated. A working model for the androgen-dependent synthesis of this fertility antigen is proposed in this study. A unique feature of the model is that the synthesis of this fertility antigen may be regulated at the level of its own messenger RNA (mRNA). He further hypothesizes that the rate at which this fertility antigen is synthesized in cells of the epididymis is controlled by proteins that bind to its mRNA. If this hypothesis proves correct, it may be possible in the near future to develop a compound that can selectively block (contraceptive) or enhance (conception) the synthesis of the fertility antigen. ***

小行星9511822 在所有的雄性哺乳动物物种中，包括人类，离开睾丸的精子是不育和不动的。精子受精能力和活力的获得发生在一个称为附睾的器官中，整个过程通常被称为“精子成熟”。目前生殖生物学和生物化学普遍认为精子成熟是由称为育性抗原的蛋白质和糖蛋白介导的。这些生育抗原由附睾在雄性激素睾酮的控制下分泌。使用大鼠作为实验模型，Hall博士已经确定了一种由附睾分泌并与精子质膜结合的关键生育抗原。这种由附睾合成的精子质膜抗原在精子表面质膜变化中起着关键的生理作用，这些质膜变化伴随着哺乳动物的精子能力和运动能力的发展。阐明男性不育的基本原因或开发作为潜在男性避孕药的化合物的第一步是了解这些生育抗原在哺乳动物附睾中是如何调节的。因此，本研究的广泛的，长期的目标是提供一个基本的了解生育抗原是如何调节的。在这项研究中提出了一个工作模型的雄激素依赖性合成的生育抗原。该模型的一个独特特征是，这种生育抗原的合成可以在其自身的信使RNA（mRNA）水平上进行调节。他进一步假设，这种生育抗原在附睾细胞中的合成速率是由与其mRNA结合的蛋白质控制的。如果这一假设被证明是正确的，那么在不久的将来就有可能开发出一种化合物，可以选择性地阻断（避孕）或增强（受孕）生育抗原的合成。 ***