Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Center of Excellence in Environmental Toxicology & Department of Systems Pharmacology & Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, 421 Curie Boulevard, PA 19104-6160, Philadelphia, USA.
Pharmacol Res. 2020 Feb;152:104446. doi: 10.1016/j.phrs.2019.104446. Epub 2019 Sep 20.
Endometriosis is a common gynecological disorder, which is treated surgically and/ or pharmacologically with an unmet clinical need for new therapeutics. A completed phase I trial and a recent phase II trial that investigated the steroidal aldo-keto reductase 1C3 (AKR1C3) inhibitor BAY1128688 in endometriosis patients prompted this critical assessment on the role of AKR1C3 in endometriosis. This review includes an introduction to endometriosis with emphasis on the roles of prostaglandins and progesterone in its pathophysiology. This is followed by an overview of the major enzymatic activities and physiological functions of AKR1C3 and of the data published to date on the expression of AKR1C3 in endometriosis at the mRNA and protein levels. The review concludes with the rationale for using AKR1C3 inhibitors, a discussion of the effects of AKR1C3 inhibition on the pathophysiology of endometriosis and a brief overview of other drugs under clinical investigation for this indication.
子宫内膜异位症是一种常见的妇科疾病，临床上采用手术和/或药物治疗，但仍需要新的治疗方法。一项 I 期临床试验和最近的一项 II 期临床试验研究了甾体aldo-keto 还原酶 1C3（AKR1C3）抑制剂 BAY1128688 在子宫内膜异位症患者中的作用，这促使我们对 AKR1C3 在子宫内膜异位症中的作用进行了批判性评估。本综述包括对子宫内膜异位症的介绍，重点介绍前列腺素和孕激素在其病理生理学中的作用。接下来是对 AKR1C3 的主要酶活性和生理功能以及迄今为止发表的 AKR1C3 在子宫内膜异位症 mRNA 和蛋白质水平表达的数据的概述。综述最后阐述了使用 AKR1C3 抑制剂的基本原理，讨论了 AKR1C3 抑制对子宫内膜异位症病理生理学的影响，并简要概述了其他正在为此适应症进行临床研究的药物。
