MEMBRANE ASSOCIATED STEROID RECEPTORS

膜相关类固醇受体

• 批准号: 6106769
• 负责人: E M EDDY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6106769
• 关键词: acrosome; laboratory mouse; male; membrane structure; molecular cloning; progesterone receptors; reproduction; testis; yeast two hybrid system

Steroid receptors typically are ligand-dependent transcription factors that modulate expression of specific genes by binding to promoter elements. However, steroid hormones also appear to bind to membrane-associated receptors to induce rapid activation of signal transduction pathways in the absence of changes in gene transcription. Progesterone is believed to act through such receptors to activate Xenopus oocyte maturation and to rapidly stimulate calcium influx and chloride efflux to trigger the acrosome reaction in human sperm. These receptors have not been identified, but a cDNA believed to encode a porcine membrane-associated progesterone receptor (MAPR) has been reported recently. We have cloned the homologous mouse cDNA and used it and antisera to two deduced peptide sequences that it encodes to determine the distribution of the transcript and protein in the male reproductive system. A 1.8 kb transcript is abundant in mouse testis, isolated germ cells and epididymis. The protein is present in spermatogenic cells (pachytene spermatocytes and spermatids) and Leydig cells in the testis, in epithelial cells lining the epididymis, and associated with anterior acrosome of spermatozoa. However, MAPR lacks sequence homology to steroid-binding proteins, calcium channel proteins, or tyrosine kinases. The porcine cDNA encoded a component of a progesterone-binding complex and we hypothesize that other proteins in the complex provide these functions. This hypothesis is being tested with a yeast two-hybrid screening approach, using MAPR as the bait to identify other proteins that associate with this component.

类固醇受体通常是配体依赖的 转录因子通过以下方式调节特定基因的表达 与启动子元件结合。然而，类固醇激素也 似乎与膜相关受体结合，从而快速诱导 在没有变化的情况下激活信号转导通路 在基因转录中。黄体酮被认为通过这种方式发挥作用 激活非洲爪哇卵母细胞成熟和快速成熟的受体 刺激钙离子内流和氯离子外流以触发顶体 人类精子中的反应。这些受体还没有确定， 但一个据信编码猪膜相关基因的cDNA. 孕激素受体(MAPR)是最近报道的一种受体。我们 克隆了小鼠同源基因，并将其与抗血清进行了比较 到它编码的两个推导的肽序列，以确定 转录本和蛋白质在雄性生殖器官中的分布 系统。分离的1.8kb转录本在小鼠睾丸中大量存在 生殖细胞和附睾。这种蛋白质存在于精子生成过程中。 细胞(粗线期精母细胞和精细胞)和间质细胞 睾丸，位于附睾壁上皮细胞内，并与 精子顶体的前部。然而，MapR缺乏 类固醇结合蛋白、钙通道的序列同源性 蛋白质，或酪氨酸激酶。猪的c DNA编码一个 黄体酮结合复合体的成分，我们假设 复合体中的其他蛋白质提供这些功能。这 这一假说正在通过酵母双杂交筛选得到验证 方法，使用MapR作为诱饵来识别其他 与此组件关联。