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Volume 15, Issue 4 (July 2013) 15, 487–491; 10.1038/aja.2013.26

The effect of diet-induced insulin resistance on DNA methylation of the androgen receptor promoter in the penile cavernosal smooth muscle of mice

Jin-Wook Kim1, Mi-Mi Oh1,2, Cheol-Yong Yoon1, Jae-Hyun Bae2, Je-Jong Kim2 and Du-Geon Moon1,2

1 Department of Urology, Korea University Medical Center Guro Hospital, Seoul 152-703, Korea
2 Department of Urology, Korea University College of Medicine, Seoul 152-703, Korea

Correspondence: Dr DG Moon, (dgmoon@korea.ac.kr)

Received 14 December 2012; Revised 31 January 2013; Accepted 10 March 2013; Advance online publication 3 June 2013


Population studies have suggested an association between diabetes and the symptoms of testosterone deficiency. Recently, the expression of the androgen receptor (AR) has been shown to be decreased in diabetic patients. Furthermore, diabetes has been shown to induce global methylation. In this study, we used an animal model to investigate whether diabetes results in increased methylation of the AR promoter and whether these changes are associated with the decreased expression of AR in penile cavernosal smooth muscle tissue. Twenty C57BL/6J mice were divided into two groups, receiving either high- (mature diabetic) or low- (mature control) caloric meals for 14 weeks. Another 10 mice were killed at 1 week (young control). Animals in the mature diabetic group showed decreased testosterone levels, although this was not statistically significant. In both control groups, no significant methylation was observed in the AR promoter region CpG island (−85 to +339). In the mature diabetic group, significant methylation was observed at +185 and +200 of the AR promoter. These changes were associated with increased homeostatic model assessment for insulin resistance (HOMA-IR) and decreased corpus cavernosal tissue mass and expression of AR mRNA and protein. We conclude that in these animals, insulin resistance increased the methylation of the GC-rich regions of the AR promoter, leading to decreased AR expression.

Keywords: androgen receptor (AR); diabetes; DNA methylation

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.