MECHANISM OF ACTION OF STEROID HORMONES

我们的长期目标是了解分子和 参与启动和实施的代谢事件 每种肾上腺糖皮质激素的生物学效应。 我们在这个目标上取得了进展，因为我们发现了一个 很少(6-11)非常快速地诱导蛋白质和mRNAs 似乎启动了荷尔蒙效应在每个正常的 靶组织：胸腺、脂肪、肝脏和成纤维细胞。其中之一 其中，糖皮质激素尤其令人感兴趣，因为它是最快的 在所有靶细胞中进行诱导。另一种，蛋白质1N可能是 葡萄糖转运的生理性抑制剂和/或 脂蛋白家族。 我们正在进行的部分调查旨在提供 有关这些调解人的更详细信息，请参阅 目标单元格。对诱导机制的研究将梳理 主要和次要反应，并收集更多信息 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 不同糖皮质激素个体化诱导的特异性 以可能的子分类为目标。我们将进一步 通过观察调解人的行动来调查职能 以及亚细胞系统中对它们的抗体。 其他工作的目标是开发寡核苷酸和 抗体探针。然后，从糖皮质激素开始，我们将 进行分子克隆。除了结构上的 关于这些蛋白质及其基因的信息这将是 允许最终使用表达载体来进一步 探索它们在培养细胞中的功能。 临床相关性。治疗方面的好处是 丹参的免疫抑制和抗炎作用 糖皮质激素在慢性病状态和器官中的应用 移植和癌症化疗被生命所抵消- 骨吸收和结缔组织的威胁副作用 浪费。似乎很可能是个人的调解人 糖皮质激素作用本身或相关治疗药物 由基因工程衍生出来的最终将可用于 生产糖皮质激素理想作用的临床医生 没有这些不幸的副作用。这些研究还将 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 对艾滋病的研究具有相关性。

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.