11-ketotestosterone is a major androgen produced in human gonads

Yoshitaka Imamichi, Koh Ichi Yuhki, Makoto Orisaka, Takeshi Kitano, Kuniaki Mukai, Fumitaka Ushikubi, Takanobu Taniguchi, Akihiro Umezawa, Kaoru Miyamoto, Takashi Yazawa

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)3582-3591
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

Fingerprint

Gonads
Androgens
MCF-7 Cells
Testosterone
Leydig Cells
11-beta-Hydroxysteroid Dehydrogenases
Cell proliferation
Plasmas
Estrogen Receptors
11-ketotestosterone
Cytochrome P-450 Enzyme System
Transcriptional Activation
Estrogens
Cell Proliferation
Theca Cells
Aromatase
Androgen Receptors
Luciferases
Sex Characteristics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Imamichi, Y., Yuhki, K. I., Orisaka, M., Kitano, T., Mukai, K., Ushikubi, F., ... Yazawa, T. (2016). 11-ketotestosterone is a major androgen produced in human gonads. Journal of Clinical Endocrinology and Metabolism, 101(10), 3582-3591. https://doi.org/10.1210/jc.2016-2311

11-ketotestosterone is a major androgen produced in human gonads. / Imamichi, Yoshitaka; Yuhki, Koh Ichi; Orisaka, Makoto; Kitano, Takeshi; Mukai, Kuniaki; Ushikubi, Fumitaka; Taniguchi, Takanobu; Umezawa, Akihiro; Miyamoto, Kaoru; Yazawa, Takashi.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 10, 01.10.2016, p. 3582-3591.

Research output: Contribution to journalArticle

Imamichi, Y, Yuhki, KI, Orisaka, M, Kitano, T, Mukai, K, Ushikubi, F, Taniguchi, T, Umezawa, A, Miyamoto, K & Yazawa, T 2016, '11-ketotestosterone is a major androgen produced in human gonads', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 10, pp. 3582-3591. https://doi.org/10.1210/jc.2016-2311
Imamichi, Yoshitaka ; Yuhki, Koh Ichi ; Orisaka, Makoto ; Kitano, Takeshi ; Mukai, Kuniaki ; Ushikubi, Fumitaka ; Taniguchi, Takanobu ; Umezawa, Akihiro ; Miyamoto, Kaoru ; Yazawa, Takashi. / 11-ketotestosterone is a major androgen produced in human gonads. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 10. pp. 3582-3591.
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AU - Mukai, Kuniaki

AU - Ushikubi, Fumitaka

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