一种新型雄烯二酮衍生物14α-羟基-4-雄烯-3,6,17-三酮（14α-OHAT）对人子宫肿瘤芳香化酶活性的抑制作用

Inhibitory effect of a new androstenedione derivative, 14 alpha-hydroxy-4-androstene-3,6,17-trione (14 alpha-OHAT) on aromatase activity of human uterine tumors.

作者信息

Yamamoto T, Fukuoka M, Fujimoto Y, Kitawaki J, Nakakoshi M, Yoshihama M, Okada H

机构信息

Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Japan.

出版信息

J Steroid Biochem. 1990 Aug 28;36(6):517-21. doi: 10.1016/0022-4731(90)90167-q.

DOI:10.1016/0022-4731(90)90167-q

PMID:2214767

Abstract

The development of human uterine estrogen-dependent tumors is considered to be closely related to estrogen biosynthesis. This study examined whether or not 14 alpha-hydroxy-4-androstene-3,6,17-trione (14 alpha-OHAT), a new 4-androstene-3, 17-dione derivative synthesized microbiologically, inhibits estrogen biosynthetase (aromatase) activities of human uterine tumors (i.e. uterine endometrial cancer, uterine leiomyoma and uterine adenomyosis tissues). 14 alpha-OHAT inhibited aromatase activity in all uterine tumors, dose-dependently (0.1-10 microM). Moreover, 14 alpha-OHAT did not show the binding affinity to rabbit uterine cytosol-sex steroids, and it was not converted to estrogen in human placental preparations. Thus, 14 alpha-OHAT, an aromatase inhibitor, may be useful clinically as an endocrine chemotherapy for peri- or post-menopausal women with uterine estrogen-dependent tumors.

摘要

人类子宫雌激素依赖性肿瘤的发展被认为与雌激素生物合成密切相关。本研究检测了经微生物合成的新型4-雄烯-3,17-二酮衍生物14α-羟基-4-雄烯-3,6,17-三酮（14α-OHAT）是否抑制人类子宫肿瘤（即子宫内膜癌、子宫平滑肌瘤和子宫腺肌病组织）的雌激素生物合成酶（芳香化酶）活性。14α-OHAT在所有子宫肿瘤中均剂量依赖性地抑制芳香化酶活性（0.1 - 10 microM）。此外，14α-OHAT对兔子宫胞液性类固醇没有结合亲和力，且在人胎盘制剂中不会转化为雌激素。因此，芳香化酶抑制剂14α-OHAT可能在临床上作为内分泌化疗药物，用于治疗患有子宫雌激素依赖性肿瘤的围绝经期或绝经后妇女。