SEX STEROID-BINDING PROTEIN AND ANDROGEN ACTION

性类固醇结合蛋白和雄激素作用

• 批准号: 3313731
• 负责人: DAVID A DAMASSA
• 金额: $ 18.39万
• 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/3313731
• 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剂， 无论是男性还是女性。 在胎儿期存在于循环中 在人类发育过程中，SBP活性在出生后显著增加 期 有趣的是，在男性中， 睾酮（T）与大百分比的循环T结合， 收缩压 尽管长期以来人们认识到，不与SBP结合的T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 在靶细胞水平上作为单独的内分泌信号。 我们 长期研究目标是：1）确定SBP在以下方面的作用： 雄激素的作用和2）确定的因素负责 该蛋白质的合成/分泌的生理调节。 的 这一特定项目期间的目标是确定SBP对以下方面的影响： 男性性分化的研究，并确定SBP基因的控制因素 在出生后的表现。 这些调查正在 在Djungarian仓鼠和小棕色蝙蝠中进行， 像人类一样，在收缩压和舒张压方面都表现出明显的增加， 它与存在于细胞中的2kb RNA特异性杂交， 出生后的准噶尔仓鼠肝脏。 使用这种探针以及抗血清 其将产生纯化的杨氏仓鼠SBP（DhSBP）， 将定义SBP基因表达的出生后变化，并将cDNA文库 筛选以获得DhSBP的克隆。 这些克隆人将 测序并用于产生核糖核苷酸探针以分析 控制出生后SBP的组织/细胞特异性表达 发展 还将进行实验来描述性 标记SBP的组织特异性结合和摄取与 确定T对这些过程的影响。 收缩压的影响， 雄激素的吸收和代谢在出生后期间和 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 关于SBP的生理控制和 SBP在雄激素作用中的作用。