Zhang Li, Lei Da, Zhu Gui-Ping, Hong Lei, Wu Sai-Zhu
Department of Cardiology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
Chin Med Sci J. 2013 Jun;28(2):88-94. doi: 10.1016/s1001-9294(13)60028-0.
To determine whether testosterone modulates markers of cardiomyocytes aging via its classic androgen receptor (AR)-dependent pathway or conversion to estradiol.
Male littermates and testicular feminized (Tfm) mice were randomly separated into 4 experimental groups littermate controls (n=8), Tfm mice (n=7), testosterone-treated Tfm mice (n=8), and Tfm mice treated with testosterone in combination with the aromatase inhibitor anastrazole (n=7). Cardiomyocytes were isolated from mouse left ventricles, the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the amount of malondialdehyde (MDA) were measured using colorimetry method, and expression of p16(INK4α) and retinoblastoma (Rb) proteins were detected by Western blotting.
The SOD and GSH-Px enzyme activities of cardiomyocytes were decreased, and the MDA levels and the expression of p16(INK4α) and Rb proteins were increased in Tfm mice compared with control mice. An increase was observed in the activities of SOD and GSH-Px enzyme as well as a decrease in MDA levels and the expression of p16(INK4α) and Rb proteins in the testosterone-treated Tfm mice. After co-treatment with anastrazole in Tfm mice, these improvement were partly inhibited.
Physiological testosterone replacement can delay cardiomyocyte aging in Tfm mice, an effect that is independent of the AR pathway and in part conversion to estradiol.
确定睾酮是否通过其经典的雄激素受体（AR）依赖性途径或转化为雌二醇来调节心肌细胞衰老标志物。
将雄性同窝小鼠和睾丸雌性化（Tfm）小鼠随机分为4个实验组：同窝对照小鼠（n = 8）、Tfm小鼠（n = 7）、睾酮处理的Tfm小鼠（n = 8）以及睾酮与芳香化酶抑制剂阿那曲唑联合处理的Tfm小鼠（n = 7）。从小鼠左心室分离心肌细胞，采用比色法测定超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性以及丙二醛（MDA）的含量，并通过蛋白质印迹法检测p16（INK4α）和视网膜母细胞瘤（Rb）蛋白的表达。
与对照小鼠相比，Tfm小鼠心肌细胞的SOD和GSH-Px酶活性降低，MDA水平以及p16（INK4α）和Rb蛋白的表达增加。在睾酮处理的Tfm小鼠中，观察到SOD和GSH-Px酶活性增加，MDA水平以及p16（INK4α）和Rb蛋白的表达降低。在Tfm小鼠中与阿那曲唑联合处理后，这些改善部分受到抑制。
生理剂量的睾酮替代可延缓Tfm小鼠心肌细胞衰老，这种作用独立于AR途径且部分与转化为雌二醇无关。
