Institute for Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany.
J Steroid Biochem Mol Biol. 2012 Jan;128(1-2):29-37. doi: 10.1016/j.jsbmb.2011.09.009. Epub 2011 Oct 13.
Aging is often associated with weight gain caused by metabolic changes including an increase of body fat. In this study we assessed the impact of age on estrogen responsiveness in the uterus and adipose tissue (AT) in aromatase-knockout (ArKO) mice. ArKO mice at the age of three or twelve months respectively were treated s.c. with vehicle, E(2) (10 μg/kg BW/d) or genistein (15 mg/kg BW/d) for three days. In the ArKO mouse model we were able to demonstrate that estrogen treatment resulted in an age specific response pattern both on a physiological and molecular level. Assessment of basal gene expression levels revealed significant age dependent differences only for elevated Esr1 levels in the uterus and leptin levels in infrarenal fat as well as lower levels of Pparg in the gonadal fat tissue. Investigating age dependency of estrogen responsiveness we were able to show that the E(2) and genistein resulted in age related pattern of regulation of expression of Esr1 and Lep in infrarenal and gonadal AT as well as the uterine expression of Pgr, Ltf and Pparg. In conclusion, evidence is provided that aging has an impact on the effectiveness of estrogen regulated processes in uterus and AT of ArKO mice. It remains to be elucidated whether or not this is associated with weight gain caused by an increase in body fat mass.
衰老是体重增加的常见原因，这是由代谢变化引起的，包括体脂肪增加。在这项研究中，我们评估了年龄对芳香酶敲除（ArKO）小鼠子宫和脂肪组织（AT）中雌激素反应的影响。分别将 3 月龄和 12 月龄的 ArKO 小鼠皮下注射 vehicle、E2（10 μg/kg BW/d）或金雀异黄素（15 mg/kg BW/d），连续 3 天。在 ArKO 小鼠模型中，我们能够证明雌激素治疗在生理和分子水平上都表现出年龄特异性的反应模式。基础基因表达水平的评估仅显示出显著的年龄依赖性差异，表现在子宫中 Esr1 水平升高，肾下脂肪中瘦素水平升高，以及卵巢脂肪组织中 Pparg 水平降低。研究雌激素反应的年龄依赖性，我们能够表明 E2 和金雀异黄素导致了肾下和卵巢 AT 中 Esr1 和 Lep 以及子宫中 Pgr、Ltf 和 Pparg 的表达的与年龄相关的调节模式。总之，有证据表明衰老对 ArKO 小鼠子宫和 AT 中雌激素调节过程的有效性有影响。尚不清楚这是否与体脂肪增加引起的体重增加有关。
