Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice
| Autor: | Sharyn Leanne Bayne, Evan R. Simpson, Alexander R. Pinto, He Li, Jun-Ping Liu, Margaret E. E. Jones |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Telomerase medicine.drug_class Gene Expression Mice Transgenic Mice Internal medicine Adrenal Glands medicine Animals Telomerase reverse transcriptase Aromatase Molecular Biology Cellular Senescence Cell Proliferation biology Adrenal gland Adrenal cortex Estrogens Cell Biology Telomere medicine.anatomical_structure Endocrinology Estrogen biology.protein Adrenal Cortex Female Estrogen receptor alpha hormones hormone substitutes and hormone antagonists |
| Zdroj: | Cell research. 18(11) |
| ISSN: | 1748-7838 |
| Popis: | Estrogen deficiency mediates aging, but the underlying mechanism remains to be fully determined. We report here that estrogen deficiency caused by targeted disruption of aromatase in mice results in significant inhibition of telomerase activity in the adrenal gland in vivo. Gene expression analysis showed that, in the absence of estrogen, telomerase reverse transcriptase (TERT) gene expression is reduced in association with compromised cell proliferation in the adrenal gland cortex and adrenal atrophy. Stem cells positive in c-kit are identified to populate in the parenchyma of adrenal cortex. Analysis of telomeres revealed that estrogen deficiency results in significantly shorter telomeres in the adrenal cortex than that in wild-type (WT) control mice. To further establish the causal effects of estrogen, we conducted an estrogen replacement therapy in these estrogen-deficient animals. Administration of estrogen for 3 weeks restores TERT gene expression, telomerase activity and cell proliferation in estrogen-deficient mice. Thus, our data show for the first time that estrogen deficiency causes inhibitions of TERT gene expression, telomerase activity, telomere maintenance, and cell proliferation in the adrenal gland of mice in vivo, suggesting that telomerase inhibition and telomere shortening may mediate cell proliferation arrest in the adrenal gland, thus contributing to estrogen deficiency-induced aging under physiological conditions. |
| Databáze: | OpenAIRE |
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