Watanabe S, Tohma Y, Chiba H, Shimizu Y, Saito H, Yanaihara T
Department of Obstetrics and Gynecology, Showa University, School of Medicine, Tokyo, Japan.
Endocr J. 1994 Aug;41(4):421-7. doi: 10.1507/endocrj.41.421.
19-Hydroxyandrogens are known to be an intermediary metabolite in the aromatizing reaction, though the physiological role of this compound has not yet been clarified. In this study, microsomes obtained from human corpus luteum were incubated with testosterone or 19-hydroxytestosterone (19-OHT) as the substrate to investigate the biochemical significance of 19-OHT in the process of aromatization in the ovary. The inhibitory effects of 4-hydroxyandrostenedione (4-OHA) on the formation of estradiol from testosterone and 19-OHT in human ovary were also investigated. When testosterone was incubated with human ovarian microsomes, 19-OHT and estradiol were identified. When 19-OHT was used as the substrate, the formation of estradiol was demonstrated. To our knowledge, this is the first report to demonstrate the formation of estradiol from 19-OHT in human ovarian tissue. The Km value of aromatase for testosterone on human corpus luteum microsomes was 0.21 microM. 4-OHA exhibited inhibition with a Ki of 35 nM. With testosterone and 19-OHT as the substrate, the formation of estradiol was also equally inhibited by 4-OHA. A dose dependent inhibition of estradiol formation was observed, with no apparent accumulation of 19-OHT. These results suggest that 19-OHT may not only be an intermediary metabolite in the aromatization of testosterone by human ovary but could be a product of the microsomal enzyme.
19-羟基雄激素被认为是芳香化反应中的一种中间代谢产物，尽管该化合物的生理作用尚未阐明。在本研究中，将从人黄体中获得的微粒体与睾酮或19-羟基睾酮（19-OHT）作为底物一起孵育，以研究19-OHT在卵巢芳香化过程中的生化意义。还研究了4-羟基雄烯二酮（4-OHA）对人卵巢中睾酮和19-OHT生成雌二醇的抑制作用。当睾酮与人卵巢微粒体一起孵育时，鉴定出了19-OHT和雌二醇。当使用19-OHT作为底物时，证明了雌二醇的生成。据我们所知，这是第一份证明人卵巢组织中由19-OHT生成雌二醇的报告。人黄体微粒体上芳香化酶对睾酮的Km值为0.21微摩尔。4-OHA表现出抑制作用，Ki为35纳摩尔。以睾酮和19-OHT作为底物时，4-OHA对雌二醇的生成也有同等程度的抑制作用。观察到雌二醇生成的剂量依赖性抑制，且没有明显的19-OHT积累。这些结果表明，19-OHT不仅可能是人卵巢中睾酮芳香化的中间代谢产物，还可能是微粒体酶的产物。
