Bird C E, Masters V, Sterns E E, Clark A F
Cancer Res. 1982 Nov;42(11):4797-800.
delta-5-Androstene-3 beta, 17 beta-diol has potential estrogenic activity because it is known to bind to receptors and translocate to the nucleus of certain estrogen target tissues. Its role in the biology of breast cancer is unclear. Aminoglutethimide plus hydrocortisone ("medical adrenalectomy") has been used to treat postmenopausal women with metastatic breast cancer. We studied delta 5-androstene-3 beta, 17 beta-diol metabolism in postmenopausal women with breast cancer before and during aminoglutethimide-plus-hydrocortisone therapy, utilizing the constant infusion technique. The metabolic clearance rate for five subjects was 799 +/- 89 liters/24 hr (470 +/- 47 liters/24 hr/sq m) before and 751 +/- 93 liters/24 hr (444 +/- 57 liters/24 hr/sq m) during therapy. Plasma delta 5-androstene-3 beta, 17 beta-diol and delta 5-androstene-3 beta, 17 beta-diol free index decreased despite absence of change in the metabolic clearance rate. Increased dehydroepiandrosterone/delta 5-androstene-3 beta, 17 beta-diol conversion ratios in individual patients suggested an increase in 17 beta-hydroxysteroid dehydrogenase activity during therapy. There were no alterations in the formation of the estrogen precursors testosterone and delta 4-androstene-3,17-dione.
Δ5-雄烯-3β,17β-二醇具有潜在的雌激素活性，因为已知它能与受体结合并转移至某些雌激素靶组织的细胞核。其在乳腺癌生物学中的作用尚不清楚。氨鲁米特加氢化可的松（“药物性肾上腺切除术”）已被用于治疗绝经后转移性乳腺癌妇女。我们采用持续输注技术，研究了氨鲁米特加氢化可的松治疗前和治疗期间绝经后乳腺癌妇女体内Δ5-雄烯-3β,17β-二醇的代谢情况。5名受试者治疗前的代谢清除率为799±89升/24小时（470±47升/24小时/平方米），治疗期间为751±93升/24小时（444±57升/24小时/平方米）。尽管代谢清除率没有变化，但血浆中Δ5-雄烯-3β,17β-二醇和Δ5-雄烯-3β,17β-二醇游离指数却下降了。个别患者中脱氢表雄酮/Δ5-雄烯-3β,17β-二醇转化率增加，提示治疗期间17β-羟类固醇脱氢酶活性增强。雌激素前体睾酮和Δ4-雄烯-3,17-二酮的生成没有改变。
