MECHANISM OF ACTION OF STEROID HORMONES

类固醇激素的作用机制

• 批准号: 3225551
• 负责人: DONALD A YOUNG
• 金额: $ 23.73万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3225551
• 关键词: adipocytes; antibody; chickens; complementary DNA; corticosterone; dexamethasone; fibroblasts; gel electrophoresis; gene expression; gene induction /repression; genetic translation; glucocorticoids; glucose transport; glycoproteins; laboratory mouse; laboratory rat; liver cells; messenger RNA; molecular cloning; nucleic acid hybridization; phospholipase inhibitor; protein biosynthesis; steroid hormone metabolism; steroid hormone receptor; thymus; tissue /cell culture

The long-term objectives are to understand the molecular and metabolic events involved in the initiation and implementation of each of the biological effects of adrenal glucocorticoid hormones. We have made progress towards this goal by the discovery of a few (6-11) very rapid inductions of proteins and mRNAs that appear to initiate the hormone effects in each of the normal target tissues; thymus, fat, liver and fibroblastic cells. One of these, glucocortin, is of special interest as the most rapid induction in all target cells. Another, protein 1N may be the physiological inhibitor of glucose transport and/or a member of the lipocortin family. Portions of our continuing investigations are aimed providing more detailed information about these mediators in the different target cells. Studies on induction mechanisms will sort out primary and secondary responses and gather further information about subcellular locations, DNA binding, and structural relationships with other molecules. We will investigate the specificity of individual inductions for a variety of glucocorticoids with aim of possible sub-classifications. We will further investigate functions by observing the actions of the mediators themselves and antibodies to them in subcellar systems. Other work is aimed at the development of oligonucleotide and antibody probes. Then, starting with glucocortin we will undertake molecular cloning. In addition to the structural information gained about these proteins and their genes this will allow the eventual use of expression vectors for the further exploration of their functions in cultured cells. Clinical relevance. The therapeutic benefits that immunosuppressive and anti-inflammatory effects of glucocorticoids offer in chronic disease states, organ transplantation, and cancer chemotherapy are offset by the life- threatening side effects of bone resorption and connective tissue wasting. It seems likely that mediators of the individual glucocorticoid actions themselves or related therapeutic agents derived by genetic engineering will eventually be available to the clinician for the production of desirable actions of glucocorticoids without these unfortunate side effects. These studies will also provide fundamental information about bioregulatory mechanisms in thymus cells; so the fundamental information may eventually have relevance to research on AIDS.

长期目标是了解分子和 代谢事件涉及启动和实施 肾上腺糖皮质激素的每种生物效应。 我们在实现这一目标方面取得了进展，发现了 很少 (6-11) 非常快速地诱导蛋白质和 mRNA 似乎会在每种正常情况下启动激素效应 靶组织；胸腺、脂肪、肝脏和成纤维细胞。 之一 这些糖皮质素作为最快速的药物而受到特别关注。 所有靶细胞中的诱导。 另外，蛋白质 1N 可能是 葡萄糖转运的生理抑制剂和/或成员 脂皮质素家族。 我们持续调查的部分目的是提供 有关这些调解员的更多详细信息 靶细胞。 诱导机制研究将理清 主要和次要反应并收集进一步的信息 关于亚细胞位置、DNA 结合和结构 与其他分子的关系。 我们将调查 各种糖皮质激素个体诱导的特异性 以可能的子分类为目标。 我们将进一步 通过观察中介者的行为来研究功能 自身以及亚细胞系统中针对它们的抗体。 其他工作旨在开发寡核苷酸和 抗体探针。 然后，从糖皮质素开始，我们将 进行分子克隆。 除了结构上的 获得有关这些蛋白质及其基因的信息，这将 允许最终使用表达载体进行进一步的研究 探索它们在培养细胞中的功能。 临床相关性。 其治疗益处是 免疫抑制和抗炎作用 糖皮质激素在慢性疾病状态、器官 移植和癌症化疗被生命所抵消 骨吸收和结缔组织的威胁性副作用 浪费。 个人的调解者似乎很可能 糖皮质激素本身或相关治疗剂的作用 由基因工程衍生的最终将可供人类使用 临床医生产生所需的糖皮质激素作用 没有这些不幸的副作用。 这些研究也将 提供有关生物调节机制的基本信息 在胸腺细胞中；所以基本信息最终可能 与艾滋病研究相关。