Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway
The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradi...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2011-11-01
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| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011001100007&lng=en&tlng=en |
| _version_ | 1818062511144960000 |
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| author | L. Zhang S.Z. Wu Y.J. Ruan L. Hong X.W. Xing W.Y. Lai |
| author_facet | L. Zhang S.Z. Wu Y.J. Ruan L. Hong X.W. Xing W.Y. Lai |
| author_sort | L. Zhang |
| collection | DOAJ |
| description | The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol. |
| first_indexed | 2024-12-10T14:05:22Z |
| format | Article |
| id | doaj.art-3e701cb71e17477aa7d86a9ad858fe51 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-12-10T14:05:22Z |
| publishDate | 2011-11-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-3e701cb71e17477aa7d86a9ad858fe512022-12-22T01:45:41ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2011-11-0144111118112410.1590/S0100-879X2011001100007S0100-879X2011001100007Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathwayL. Zhang0S.Z. Wu1Y.J. Ruan2L. Hong3X.W. Xing4W.Y. Lai5Southern Medical UniversitySouthern Medical UniversityGuangzhou Military Area Command of Chinese PLASouthern Medical UniversityThe First Affiliated Hospital of Guangzhou Medical CollegeSouthern Medical UniversityThe testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011001100007&lng=en&tlng=enAgingTestosteroneCardiomyocyteAndrogen receptorEstradiolTfm mice |
| spellingShingle | L. Zhang S.Z. Wu Y.J. Ruan L. Hong X.W. Xing W.Y. Lai Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway Brazilian Journal of Medical and Biological Research Aging Testosterone Cardiomyocyte Androgen receptor Estradiol Tfm mice |
| title | Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway |
| title_full | Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway |
| title_fullStr | Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway |
| title_full_unstemmed | Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway |
| title_short | Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway |
| title_sort | testosterone therapy delays cardiomyocyte aging via an androgen receptor independent pathway |
| topic | Aging Testosterone Cardiomyocyte Androgen receptor Estradiol Tfm mice |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011001100007&lng=en&tlng=en |
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