Objective To determine whether testosterone modulates markers of cardiomyocytes aging via its classic androgen receptor （AR）-dependent pathway or conversion to estradiol. Methods Male littermates and testicular fem...Objective To determine whether testosterone modulates markers of cardiomyocytes aging via its classic androgen receptor （AR）-dependent pathway or conversion to estradiol. Methods 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 us- ing colorimetry method, and expression of p l 6~NKga and retinoblastoma （Rb） proteins were detected by Western blotting. Results The SOD and GSH-Px enzyme activities of cardiomyocytes were decreased, and the MDA levels and the expression of p l 6INK＊a 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 p 16~NK4a and Rb proteins in the testosterone-treated Tfm mice. After co-treatment with anastrazole in Tfm mice, these improvement were partly inhib- ited. Conclusion 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.展开更多
基金Supported by National Basic Research Program of China(973 Program,2007CB507404)
文摘Objective To determine whether testosterone modulates markers of cardiomyocytes aging via its classic androgen receptor （AR）-dependent pathway or conversion to estradiol. Methods 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 us- ing colorimetry method, and expression of p l 6~NKga and retinoblastoma （Rb） proteins were detected by Western blotting. Results The SOD and GSH-Px enzyme activities of cardiomyocytes were decreased, and the MDA levels and the expression of p l 6INK＊a 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 p 16~NK4a and Rb proteins in the testosterone-treated Tfm mice. After co-treatment with anastrazole in Tfm mice, these improvement were partly inhib- ited. Conclusion 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.
