Wang Jing, Dai Shu, Guo Yan, Xie Wen, Zhai Yonggong
Beijing Key Laboratory of Gene Resource and Molecular Development and College of Life Sciences, Beijing Normal University, Beijing 100875, P.R. China.
Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, PA 15261, Pittsburgh ; Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P.R. China.
EXCLI J. 2014 Jul 7;13:728-39. eCollection 2014.
Hormonal homeostasis is essential for a variety of physiological and pathological processes. Elimination and detoxification of xenobiotics, such as drugs introduced into the human body, could disrupt the balance of hormones due to the induction of drug metabolizing enzymes (DMEs) and transporters. Pregnane X receptor (PXR, NR1I2) functions as a master xenobiotic receptor involved in drug metabolism and drug-drug interactions by its coordinated transcriptional regulation of phase I and phase II DMEs and transporters. Recently, increasing evidences indicate that PXR can also mediate the endocrine disruptor function and thus impact the integrity of the endocrine system. This review focuses primarily on the recent advances in our understanding of the function of PXR in glucocorticoid, mineralocorticoid, androgen and estrogen homeostasis. The elucidation of PXR-mediated drug-hormone interactions might have important therapeutic implications in dealing with hormone-dependent diseases and safety assessment of drugs.
激素稳态对于多种生理和病理过程至关重要。外源性物质（如引入人体的药物）的消除和解毒，可能会因诱导药物代谢酶（DMEs）和转运体而破坏激素平衡。孕烷X受体（PXR，NR1I2）作为主要的外源性物质受体，通过其对I相和II相DMEs以及转运体的协调转录调控，参与药物代谢和药物 - 药物相互作用。最近，越来越多的证据表明，PXR还可以介导内分泌干扰功能，从而影响内分泌系统的完整性。本综述主要关注我们对PXR在糖皮质激素、盐皮质激素、雄激素和雌激素稳态功能理解的最新进展。阐明PXR介导的药物 - 激素相互作用可能对治疗激素依赖性疾病和药物安全性评估具有重要的治疗意义。
