Developmental Differences in Brain Androgen Synthesis

大脑雄激素合成的发育差异

• 批准号: 6671466
• 负责人: SARAH E LONDON
• 金额: $ 2.68万
• 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/6671466
• 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）：斑胸草雀鸣叫系统包括 性二形核。早期雌激素治疗使端脑男性化 遗传女性中的宋核，但阻断雌激素不会使男性化 这些细胞核存在于遗传男性中。研究表明，存在一种 大脑固有的遗传因素是歌曲男性模式的基础 系统组织。最近，性别差异出现了 17 α 羟化酶 (CYP 17) 的转录水平，该酶使 雄激素，存在于发育中的斑胸草雀的端脑中。据推测 GYP 17 的表达贯穿了歌曲的类固醇敏感期 系统发育，分布在宋核附近。这将是 使用原位杂交进行研究。据推测，不同 CYP17 mRNA 水平反映了蛋白质介导的性别差异 转录调控。 CYP 17 启动子区域的 DNA 序列 基因将通过筛选cDNA文库来确定，执行5？种族，和 筛选斑胸草雀基因组文库。这代表了第一步 鉴定差异调节 CYP17 转录的因素 发育中的雄性和雌性斑胸草雀的端脑。他们还将 表明其他疾病中雄激素合成的潜在调节机制 物种，包括人类。