Bonney R C, Reed M J, James V H
J Steroid Biochem. 1983 Jan;18(1):59-64. doi: 10.1016/0022-4731(83)90331-x.
The effect of dehydroepiandrosterone sulphate (DHA-S) and its metabolites dehydroepiandrosterone (DHA) and 5-androstene-3 beta, 17 beta-diol (ADIOL) on the activity of 17 beta-hydroxysteroid dehydrogenase in human endometrial tissue was investigated by an isotope ratio technique. The apparent KM for oestradiol was 1.59 X 10(-6) M. All three androgens inhibited the metabolism of oestradiol and the apparent Ki values were: ADIOL, 2.05 X 10(-6) M; DHA-S and DHA, 1.59 X 10(-6) M. However, ADIOL acted by direct competition with oestradiol for the active enzyme site whereas inhibition by DHA and its sulphate was non-competitive. DHA-S and DHA were more potent inhibitors of oestradiol metabolism than was ADIOL. These results support the hypothesis that adrenal androgens could be involved in the development of endometrial hyperplasia and adenocarcinoma. Inhibition of oestradiol metabolism could increase the concentration of oestradiol in endometrial tissue and if unopposed by progesterone, e.g. after the menopause or in subjects with ovulatory defects, could stimulate abnormal endometrial growth.
采用同位素比率技术研究了硫酸脱氢表雄酮（DHA-S）及其代谢产物脱氢表雄酮（DHA）和5-雄烯-3β,17β-二醇（ADIOL）对人子宫内膜组织中17β-羟基类固醇脱氢酶活性的影响。雌二醇的表观米氏常数为1.59×10⁻⁶M。这三种雄激素均抑制雌二醇的代谢，表观抑制常数（Ki）值分别为：ADIOL为2.05×10⁻⁶M；DHA-S和DHA为1.59×10⁻⁶M。然而，ADIOL通过与雌二醇直接竞争活性酶位点发挥作用，而DHA及其硫酸盐的抑制作用是非竞争性的。DHA-S和DHA对雌二醇代谢的抑制作用比ADIOL更强。这些结果支持肾上腺雄激素可能参与子宫内膜增生和腺癌发生发展的假说。抑制雌二醇代谢可增加子宫内膜组织中雌二醇的浓度，若没有孕酮的拮抗作用，例如在绝经后或排卵功能缺陷的患者中，可能会刺激子宫内膜异常生长。
