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閲覧数:105
ID 27428878
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タイトル 11-Ketotestosterone Is a Major Androgen Produced in Human Gonads
著者
今道, 力敬 (Imamichi, Yoshitaka)
結城, 幸一 (Yuki, Koh-ichi)
折坂, 誠 (Orisaka, Makoto)
北野, 健 (Kitano, Takeshi)
向井, 邦晃 (Mukai, Kuniaki)
牛首, 文隆 (Ushikubi, Fumitaka)
谷口, 隆信 (Taniguchi, Takanobu)
梅澤, 明弘 (Umezawa, Akihiro)
宮本, 薫 (Miyamoto, Kaoru)
矢澤, 隆志 (Yazawa, Takashi)
上位タイトル
The Journal of Clinical Endocrinology and Metabolism Vol.101, No.10  (2016. 7) ,p.3582- 3591
識別番号
ISSN
0021-972X
DOI 10.1210/jc.2016-2311
URI https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2016-2311
その他
PMID:27428878
抄録 CONTEXT:

11-ketotestosterone (11-KT) is a novel class of active androgen. However, the detail of its synthesis remains unknown for humans.
OBJECTIVE:

The objective of this study was to clarify the production and properties of 11-KT in human. Design, Participants, and Methods: Expression of cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 (key enzymes involved in the synthesis of 11-KT) were investigated in human gonads. The production of 11-KT was investigated in Leydig cells. Plasma concentrations of testosterone and 11-KT were measured in 10 women and 10 men of reproductive age. Investigation of its properties was performed using breast cancer-derived MCF-7 cells.
RESULTS:

Cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 were detected in Leydig cells and theca cells. Leydig cells produced 11-KT, and relatively high levels of plasma 11-KT were measured in both men and women. There was no sexual dimorphism in the plasma levels of 11-KT, even though testosterone levels were more than 20 times higher in men than in women. It is noteworthy that the levels of testosterone and 11-KT were similar in women. In a luciferase reporter system, 11-KT activated human androgen receptor-mediated transactivation. Conversely, 11-KT did not activate estrogen receptor-mediated transactivation in aromatase-expressed MCF-7 cells, whereas testosterone did following conversion to estrogen. 11-KT did not affect the estrogen/estrogen receptor -mediated cell proliferation of MCF-7 cells. Furthermore, it significantly inhibited cell proliferation when androgen receptor was transfected into MCF-7 cells.
CONCLUSIONS:

The current study indicates that 11-KT is produced in the gonads and represents a major androgen in human. It can potentially serve as a nonaromatizable androgen.
言語
eng
資源タイプ text
ジャンル Journal Article
著者版フラグ author
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