Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells.
Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells.
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DOI：
10.1621/nrs.11001
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Chang TM
中科院分区：
文献类型：
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作者：
Chang C;Yeh S;Lee SO;Chang TM
雄激素受体（AR）广泛表达，在许多生理和病理生理过程中发挥着多种作用。AR敲除（ARKO）小鼠模型的最新研究，特别是细胞类型或组织特异性ARKO模型，已经发现了许多AR细胞类型或组织特异性病理生理作用的小鼠，否则将无法从传统的去势和雄激素不敏感综合征的研究。因此，各种特定细胞类型中的AR在免疫细胞的产生和成熟、骨矿化和肌肉生长中起关键作用。在代谢方面，脑（特别是下丘脑）和肝脏中的AR似乎参与调节胰岛素敏感性和葡萄糖稳态。AR还在皮肤伤口愈合和心血管疾病（包括动脉粥样硬化和腹主动脉瘤）中起关键作用。本文将讨论从总的，细胞类型，或组织特异性ARKO模型获得的结果。使用这些体内小鼠模型了解AR细胞类型或组织特异性生理和病理生理作用将为揭示AR在人类中的作用提供有用的信息，并最终帮助我们通过靶向AR或其下游信号分子来开发更好的治疗方法，以对抗雄激素/AR相关疾病。
The androgen receptor (AR) is expressed ubiquitously and plays a variety of roles in a vast number of physiological and pathophysiological processes. Recent studies of AR knockout (ARKO) mouse models, particularly the cell type- or tissue-specific ARKO models, have uncovered many AR cell type- or tissue-specific pathophysiological roles in mice, which otherwise would not be delineated from conventional castration and androgen insensitivity syndrome studies. Thus, the AR in various specific cell types plays pivotal roles in production and maturation of immune cells, bone mineralization, and muscle growth. In metabolism, the ARs in brain, particularly in the hypothalamus, and the liver appear to participate in regulation of insulin sensitivity and glucose homeostasis. The AR also plays key roles in cutaneous wound healing and cardiovascular diseases, including atherosclerosis and abdominal aortic aneurysm. This article will discuss the results obtained from the total, cell type-, or tissue-specific ARKO models. The understanding of AR cell type- or tissue-specific physiological and pathophysiological roles using these in vivo mouse models will provide useful information in uncovering AR roles in humans and eventually help us to develop better therapies via targeting the AR or its downstream signaling molecules to combat androgen/AR-related diseases.