11-ketotestosterone is a major androgen produced in human gonads
Yoshitaka Imamichi The Journal of Clinical Endocrinology & Metabolism First Published Online: July 18, 2016
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 CYP11B1 and HSD11B2 (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: CYP11B1 and HSD11B2 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 (AR)-mediated transactivation. Conversely, 11-KT did not activate estrogen receptor (ER)-mediated transactivation in aromatase-expressed MCF-7 cells, whereas testosterone did following conversion to estrogen. 11-KT did not affect the estrogen/ER-mediated cell proliferation of MCF-7 cells. Furthermore, it significantly inhibited cell proliferation when AR 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 non-aromatizable androgen.
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