Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice

雌激素缺乏调停变老，但是内在的机制尚待充分坚定。我们这里报导 aromatase 的指向的混乱在老鼠引起的雌激素缺乏在 vivo 在肾上腺导致 telomerase 活动的重要抑制。基因表示分析证明当雌激素不在时， telomerase 颠倒 transcriptase (TERT ) 基因表示在肾上腺外皮和肾的萎缩与损害房间增长联合被减少。在 c 工具包积极的干细胞被识别在肾的外皮的实质占据。telomeres 的分析表明那雌激素缺乏比那在肾的外皮导致显著地更短的 telomeres 在野类型(WT ) 控制鼠标。为了推进，建立雌激素的原因的效果，我们在这些雌激素缺乏的动物进行了雌激素代替治疗。为 3 个星期的雌激素的管理在雌激素缺乏的老鼠恢复 TERT 基因表示， telomerase 活动和房间增长。因此，我们第一次，那雌激素缺乏在 vivo 在鼠标的肾上腺引起 TERT 基因表示， telomerase 活动， telomere 维护，和房间增长的抑制的数据表演，建议那 telomerase 抑制并且 telomere 弄短可以调停在肾上腺的房间增长拘捕，因此贡献雌激素在生理的条件下面的导致缺乏的老化。

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 teiomeres 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.