SEX STEROID BINDING PROTEIN AND ANDROGEN ACTION

性类固醇结合蛋白和雄激素作用

• 批准号: 3313735
• 负责人: DAVID A DAMASSA
• 金额: $ 19.22万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3313735
• 关键词: Chiroptera; RNA biosynthesis; androgen binding protein; androgens; antibody neutralization test; antiserum; autoradiography; chromatography; gene expression; genetic library; hamsters; hibernation; hormone regulation /control mechanism; human tissue; immunocytochemistry; in situ hybridization; laboratory rabbit; male reproductive system; molecular cloning; nucleic acid probes; nucleic acid sequence; radioimmunoassay; sex cycle; sex differentiation; sex hormones; steroid hormone; steroid hormone metabolism; testosterone

Sex steroid-binding protein (SBP) is a high affinity binder of androgens in both males and females. Present in the circulation during fetal development in humans, SBP activity increases markedly during the postnatal period. Interestingly, in males there is a coincident postnatal surge in testosterone (T) with a large percentage of circulating T being bound by SBP. Although it has long been recognized that T not bound to SBP can enter tissues by passive diffusion, recent studies suggest SBP-bound T may be acting as a separate endocrine signal at the target cell level. Our long-term research objectives are to 1) identify the role of SBP in androgen action and 2) identify the factors responsible for the physiological regulation of the synthesis/secretion of this protein. The aims of this specific project period are to define the effects of SBP on male sexual differentiation and to identify factors which control SBP gene expression during the postnatal period. These investigations are being conducted in the Djungarian hamster and the little brown bat, two species which, like humans, exhibit marked increases in both SBP has been synthesized and it specifically hybridizes with a 2 kb RNA present in postnatal Djungarian hamster liver. Using this probe, as well as antisera which will be generated to purified Djungarian hamster SBP (DhSBP), postnatal changes in SBP gene expression will be defined and cDNA libraries will be screened to obtain clones for DhSBP. These clones will be sequenced and used to produce ribonucleotide probes for analysis of the control of tissue/cell-specific expression of SBP during postnatal development. Experiments will also be conducted to characterize sex difference in tissue specific binding and uptake of labeled SBP and to determine the effects of T on these processes. The effects of SBP on the uptake and metabolism of androgens during the postnatal period and the physiological role of SBP-androgen interactions in male sexual differentiation will be determined. These experiments will provide important information on both the physiological control of SBP and the role of SBP in androgen action.

性类固醇结合蛋白(SBP)是一种高亲和力的雄激素结合蛋白 无论是雄性还是雌性。在胎儿时期存在于循环中 在人类发育过程中，SBP活性在出生后显著增加 句号。有趣的是，在男性中，出生后会同时出现 睾酮(T)与大比例的循环T结合在一起 SBP。尽管很早就认识到T不与SBP结合可以 通过被动扩散进入组织，最近的研究表明SBP结合的T可能 在靶细胞水平上充当单独的内分泌信号。我们的 长期研究目标是：1)确定SBP在 雄激素的作用和2)确定导致 这种蛋白质的合成/分泌的生理调节。这个 此特定项目期的目标是定义SBP对以下方面的影响 男性性别分化及SBP基因控制因素的筛选 在出生后时期的表达。这些调查正在进行中 在丛林仓鼠和小棕色蝙蝠这两个物种中进行 和人类一样，它们的SBP也有显著的上升 合成并与存在于体内的2kb RNA特异性杂交 出生后的金黄地鼠肝脏。使用该探针以及抗血清 它将被产生为纯化的毛地鼠SBP(DhSBP)， 将定义SBP基因表达的出生后变化并构建cDNA文库 将进行筛选以获得用于DhSBP的克隆。这些克隆人将是 测序并用于生产用于分析的核糖核苷酸探针 SBP在出生后组织/细胞特异性表达的调控 发展。还将进行实验，以确定性行为的特征 标记SBP和TO的组织特异性结合和摄取的差异 确定T对这些过程的影响。SBP对心脏功能的影响 雄激素的摄取和代谢在出生后和 SBP-雄激素相互作用在男性性行为中的生理作用 差异化将被确定。这些实验将提供 SBP的生理调控及其作用的重要信息 血压在雄激素作用中的作用。