Aims: One third of males with type 2 diabetes have hypogonadism, characterized by low total and free testosterone concentrations. We hypothesized that this condition is associated with a compensatory increase in the expression of androgen receptors (AR) and that testosterone replacement reverses these changes. We also measured estrogen receptor and aromatase expression.

Materials and Methods: This is a randomized double-blind placebo controlled trial. 32 hypogonadal and 32 eugonadal men with type 2 diabetes were recruited. Hypogonadal men were randomized to receive intramuscular testosterone or saline every 2 weeks for 22 weeks. We measured AR, ER and aromatase expression in peripheral blood mononuclear cells (MNC) and adipose tissue in hypogonadal and eugonadal males with type 2 diabetes at baseline and after 22 weeks of treatment in those with hypogonadism.

Results: The mRNA expression of AR, ER and aromatase in adipose tissue from hypogonadal men was significantly lower as compared to eugonadal men and it increased significantly to levels comparable to those in eugonadal patients with type 2 diabetes following testosterone treatment. AR mRNA expression was also significantly lower in MNC from hypogonadal patients compared to eugonadal T2DM patients. Testosterone administration in hypogonadal patients also restored AR mRNA and nuclear extract protein levels from MNC to that in eugonadal patients.

Conclusions: We conclude that, contrary to our hypothesis, the expression of AR, ER and aromatase is significantly diminished in hypogonadal men as compared to eugonadal men with type 2 diabetes. Following testosterone replacement, there is a reversal of these deficits.

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Diminished Androgen and Estrogen Receptors and Aromatase ...

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