Developmental Differences in Brain Androgen Synthesis

大脑雄激素合成的发育差异

• 批准号: 6446584
• 负责人: SARAH E LONDON
• 金额: $ 2.31万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6446584
• 关键词: RNase protection assay; androgens; aromatase; biological polymorphism; complementary DNA; developmental genetics; developmental neurobiology; estrogens; gender difference; gene expression; genetic library; genetic polymorphism; genetic promoter element; genetic regulation; genetic screening; genome; hydrolase; in situ hybridization; messenger RNA; neuroanatomy; neurogenesis; neurohormones; songbirds; steroid hormone biosynthesis; telencephalon; transcription factor

DESCRIPTION (provided by applicant): The zebra finch song system consists of sexually dimorphic nuclei. Early estrogen treatment masculinizes telencephalic song nuclei in genetic females, but blocking estrogen does not demasculinize these nuclei in genetic males. Studies have suggested that the existence of a genetic factor intrinsic to the brain underlies the masculine pattern of song system organization. Recently, a sex difference has been seen in transcriptional levels of 17 alpha hydroxylase (CYP 17), the enzyme that makes androgen, in the telencephalon of developing zebra finches. It is hypothesized that GYP 17 expression extends through the steroid sensitive period of song system development, and is distributed near the song nuclei. This will be investigated using in situ hybridization. It is hypothesized that the different levels of CYP17 mRNA reflect sex differences in protein-mediated transcriptional regulation. DNA sequence from the promoter region of the CYP 17 gene will be determined by screening a cDNA library, performing 5? RACE, and screening a zebra finch genomic library. This represents a first step in identifying the factors that differentially regulate CYP 17 transcription in the telencephalon of developing male and female zebra finch. They will also indicate potential regulatory mechanisms for androgen synthesis in other species, including humans.

描述（由申请人提供）：斑马芬奇歌曲系统由 性二态核。早期雌激素治疗男性化 遗传女性中的歌曲核，但阻止雌激素不会脱离 这些核在遗传雄性中。研究表明，存在 大脑固有的遗传因素是歌曲的男性模式的基础 系统组织。最近，已经看到了性别差异 17个α羟化酶（CYP 17）的转录水平，该酶使酶产生 雄激素，在发育中的斑马雀的尾脑中。它是假设的 GYP 17的表达延伸到歌曲的类固醇敏感时期 系统开发，并分布在歌曲核附近。这将是 使用原位杂交进行了研究。假设不同的 CYP17 mRNA水平反映了蛋白质介导的性别差异 转录调节。 CYP 17的启动子区域的DNA序列 基因将通过筛选cDNA库来确定，执行5？种族和 筛选斑马雀科基因组文库。这代表了第一步 确定差异调节CYP 17转录的因素 发展中心的男性和女性斑马鳍的脑脑。他们也会 指示其他在其他中的雄激素合成的调节机制 物种，包括人类。