Judd H L, Barone R M, Laufer L R, Gambone J C, Monfort S L, Lasley B L
Cancer Res. 1982 Aug;42(8 Suppl):3345s-3348s.
To evaluate the in vivo effect of delta 1-testololactone on peripheral aromatization, studies were performed on seven postmenopausal women with metastatic breast cancer. Analysis of variance indicated that there were significant increases of circulating androstenedione (p less than 0.05) and estradiol (p less than 0.001) during administration of different doses of testololactone. Androstenedione levels were increased with all doses of testololactone tested (50, 100, 250, and 500 mg every 6 hr for 14 days each), while estradiol rose with only the 250- and 500-mg dosages. With administration, there was a significant decrease of estrone (p less than 0.001) with the mean level falling from 26 +/- 3 (S.E.) to 11 +/- 2 pg/ml. The addition of adrenal suppression (dexamethasone, 1 mg nightly at 11 p.m.) significantly lowered androstenedione (p less than 0.05) but had no effect on estrone or estradiol levels. Long-term therapy (up to 6 months) with the 250-mg dosage showed continual suppression of estrone with no escape being observed. Studies to determine the reason for the increase of estradiol with testololactone suggested cross-reactivity of the antibody with in vivo metabolites of the drug. However, these possible metabolites did not bind to uterine cytosol estrogen receptors. The decrease in estrone with testololactone administration presumably explains its antitumor properties.
为评估δ1-睾内酯对周围组织芳香化作用的体内效应，对7名患有转移性乳腺癌的绝经后妇女进行了研究。方差分析表明，在给予不同剂量的睾内酯期间，循环中的雄烯二酮（p<0.05）和雌二醇（p<0.001）显著增加。所有测试剂量的睾内酯（每6小时50、100、250和500毫克，各持续14天）均使雄烯二酮水平升高，而雌二醇仅在250毫克和500毫克剂量时升高。给药后，雌酮显著降低（p<0.001），平均水平从26±3（标准误）降至11±2皮克/毫升。添加肾上腺抑制药物（地塞米松，每晚11点1毫克）可显著降低雄烯二酮（p<0.05），但对雌酮或雌二醇水平无影响。250毫克剂量的长期治疗（长达6个月）显示雌酮持续受到抑制，未观察到逃逸现象。确定睾内酯使雌二醇升高原因的研究表明，抗体与该药物的体内代谢产物存在交叉反应。然而，这些可能的代谢产物未与子宫胞质雌激素受体结合。睾内酯给药后雌酮的降低大概解释了其抗肿瘤特性。
