A UNIQUE TESTOSTERONE METABOLITE--17BETA-HYDROXY 4,6-ANDROSTADIENE-3-ONE

本研究的目的是探讨其致病机制。 地塞米松诱导的细胞色素P-450和P-450a的转换 睾酮对代谢产物17β-羟基-4，6- 雄二烯-3-酮(Delta 6T)。以前在这个实验室的工作， 这表明，德尔塔6T的形成与6-β- 羟化，提示相同的P-450同工酶(S)是 提出了一种双氢原子抽提机制 建议。丙戊酸酯的一种类似代谢物也是 据报道。这项工作的目的是测量重氢。 与减饱和机制相关的同位素效应。 选择性的氢化睾丸素衍生物正在被 合成的，并将经历代谢的 地塞米松诱导的微粒子及其衍生制剂 形成转染P-450a c-DNA的COS细胞。

The purpose of this study is to probe the mechanism by which dexamethosone inducible cytochrome P-450 and P-450a convert testosterone to the metabolite 17 beta-hydroxy-4,6- androstadiene-3-one (delta 6T). Previous work in this laboratory, which showed that delta 6T formation paralleled 6-beta- hydroxylation, suggested that the same P-450 isozyme(s) are involved and a dual hydrogen atom abstraction mechanism was proposed. An analogous metabolite of valproate has also been reported. The objective of this work is to measure the deuterium isotope effects associated with the desaturation mechanism. Selectively deuterated testosterone derivatives are being synthesized and will be subjected to metabolism by dexamethasone induced microsomes and preparations derived form COS cell cultures transfected with P-450a c-DNA.