COVALENT INTERACTIONS OF ESTROGENS IN TARGET TISSUES

了解雌二醇代谢在生物学中的作用 激素有必要了解其多种生物效应 代谢产物。 该项目涉及蜂窝 16α-羟基雌酮和2-羟基雌酮的相互作用，主要 雌二醇的代谢物具有与雌二醇不同的生物特性 母激素。 16α-羟基雌酮与以下物质形成共价键 通过希夫碱形成和随后的海恩斯形成伯氨基 重新排列。 2-羟基雌酮与亲核试剂发生强烈反应，例如 巯基也与生物分子形成共价键。 这两个过程均已被证明可以在体外与细胞成分一起进行 和体内并被认为在生理学和 雌激素作用的病理生理学。 将寻求准确信息 雌激素靶点中这种共价键形成的亚细胞位点 组织和特定生物大分子的性质 参与这些互动。 这些的生物学后果 将在体外和体内研究中探索过程 适当的实验模型。 预计这些研究将 阐明这些天然雌激素在荷尔蒙相关的作用 疾病。

To understand the role of metabolism of estradiol in the biology of the hormone it is essential to know the biological effects of its diverse metabolic products. This project is concerned with the cellular interactions of 16Alpha-hydroxyestrone and 2-hydroxyestrone, major metabolites of estradiol with biological properties distinct from those of the parent hormone. 16Alpha-hydroxyestrone forms covalent linkages with primary amino groups via Schiff base formation and subsequent Heyns rearrangement. 2-Hydroxyestrone reacts avidly with nucleophiles such as sulfhydryl groups to also form covalent bonds with biological molecules. Both processes have been shown to proceed with cellular components in vitro and in vivo and are considered to be of importance in the physiology and pathophysiology of estrogen action. Precise information will be sought on the subcellular sites of such covalent bond formation in estrogen target tissues and on the nature of the specific biological macromolecules involved in these interactions. The biological consequence of these processes will be explored in in vitro and in vivo studies employing appropriate experimental models. It is expected that these studies will shed light on the role of these natural estrogens in hormonally linked diseases.