title: The effect of diet-induced insulin resistance on DNA methylation of the androgen receptor promoter in the penile cavernosal smooth muscle of mice.
abstract: 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.
authors.affiliation: Department of Urology, Korea University Medical Center Guro Hospital, Seoul 152-703, Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Mi-Mi
authors.initials: MM
authors.lastname: Oh
authors.forename: Cheol-Yong
authors.initials: CY
authors.lastname: Yoon
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Bae
authors.forename: Je-Jong
authors.initials: JJ
authors.lastname: Kim
authors.forename: Du-Geon
authors.initials: DG
authors.lastname: Moon
mesh_terms: D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D048909:Diabetes Complications / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D020862:GC Rich Sequence / Q000235:genetics; D006706:Homeostasis / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000502:physiology*; D010413:Penis / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics*; D013739:Testosterone / Q000097:blood
chemical_list: D001786:Blood Glucose; D011944:Receptors, Androgen; D013739:Testosterone