Ghanim Husam, Dhindsa Sandeep, Abuaysheh Sanaa, Batra Manav, Kuhadiya Nitesh D, Makdissi Antoine, Chaudhuri Ajay, Dandona Paresh
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York, USA.
Division of Endocrinology, Diabetes and Metabolism, Saint Louis University, St Louis, Missouri, USA.
Eur J Endocrinol. 2018 Mar;178(3):277-283. doi: 10.1530/EJE-17-0673. Epub 2018 Jan 16.
One-third of males with type 2 diabetes (T2DM) 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.
This is a randomized double-blind placebo-controlled trial. Thirty-two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men were randomized to receive intramuscular testosterone or saline every 2 weeks for 22 weeks. We measured AR, ERα and aromatase expression in peripheral blood mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and eugonadal males with T2DM at baseline and after 22 weeks of treatment in those with hypogonadism.
The mRNA expression of 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 T2DM following testosterone treatment. mRNA expression was also significantly lower in MNC from hypogonadal patients compared to eugonadal T2DM patients. Testosterone administration in hypogonadal patients also restored mRNA and nuclear extract protein levels from MNC to that in eugonadal patients. In the skeletal muscle, AR mRNA and protein expression are lower in men with hypogonadism. Testosterone treatment restored AR expression levels to that comparable to levels in eugonadal men.
We conclude that, contrary to our hypothesis, the expression of AR, ERα 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.
三分之一的2型糖尿病（T2DM）男性存在性腺功能减退，其特征为总睾酮和游离睾酮浓度降低。我们推测这种情况与雄激素受体（AR）表达的代偿性增加有关，并且睾酮替代可逆转这些变化。我们还测量了雌激素受体和芳香化酶的表达。
这是一项随机双盲安慰剂对照试验。招募了32名性腺功能减退和32名性腺功能正常的T2DM男性。性腺功能减退的男性被随机分组，每2周接受一次肌肉注射睾酮或生理盐水，共22周。我们在基线时以及性腺功能减退患者接受22周治疗后，测量了性腺功能减退和性腺功能正常的T2DM男性外周血单核细胞（MNC）、脂肪组织和骨骼肌中AR、ERα和芳香化酶的表达。
与性腺功能正常的男性相比，性腺功能减退男性脂肪组织中AR和芳香化酶的mRNA表达显著降低，在睾酮治疗后显著增加至与性腺功能正常的T2DM患者相当的水平。与性腺功能正常的T2DM患者相比，性腺功能减退患者MNC中的AR mRNA表达也显著降低。对性腺功能减退患者给予睾酮也使MNC中的AR mRNA和核提取物蛋白水平恢复到性腺功能正常患者的水平。在骨骼肌中，性腺功能减退男性的AR mRNA和蛋白表达较低。睾酮治疗使AR表达水平恢复到与性腺功能正常男性相当的水平。
我们得出结论，与性腺功能正常的2型糖尿病男性相比，性腺功能减退男性中AR、ERα和芳香化酶的表达显著降低，这与我们的假设相反。睾酮替代后，这些缺陷得到逆转。
