Mackenzie P I, Mojarrabi B, Meech R, Hansen A
Department of Clinical Pharmacology, School of Medicine Flinders Medical Centre, South Australia, Australia.
J Endocrinol. 1996 Sep;150 Suppl:S79-86.
Under normal physiological conditions, glucuronidation generally terminates the biological activities of steroids and leads to their elimination in the bile and urine. This process is postulated to play a role in homeostasis by regulating the intracellular steady-state levels of these effector ligands. Indeed, the duration of response to specific steroid signals may be partly determined by the capacity of the cell or tissue to eliminate the steroids as unreactive glucuronides. Under pathophysiological conditions or during steroid therapies, glucuronidation may sometimes result in the formation of more biologically active or toxic metabolites as exemplified by the steroid D ring glucuronides. The degree of toxicity or biological effect in the cell exposed to these steroids will also depend on its complement of UGTs. To investigate these processes in more detail, the steroid specificities and distribution of individual UGTs in various target organs require elucidation. In this review, our current knowledge of the steroid specificities of various rat and human UGTs is described and preliminary investigations on the mechanisms governing tissue specificity are presented.
在正常生理条件下，葡萄糖醛酸化通常会终止类固醇的生物活性，并导致它们在胆汁和尿液中被清除。据推测，这一过程通过调节这些效应配体的细胞内稳态水平在体内平衡中发挥作用。事实上，对特定类固醇信号的反应持续时间可能部分取决于细胞或组织将类固醇作为无反应性葡萄糖醛酸苷清除的能力。在病理生理条件下或类固醇治疗期间，葡萄糖醛酸化有时可能会导致形成更具生物活性或毒性的代谢物，类固醇D环葡萄糖醛酸苷就是例证。暴露于这些类固醇的细胞中的毒性程度或生物学效应也将取决于其UGT的组成。为了更详细地研究这些过程，需要阐明各种靶器官中单个UGT的类固醇特异性和分布。在这篇综述中，描述了我们目前对各种大鼠和人类UGT的类固醇特异性的了解，并介绍了关于组织特异性调控机制的初步研究。
