Abstract:
Sulfatase (STS) and sulfotransferases (SULT) have important role in the biosynthesis and action of steroid hormones. STS catalyzes the hydrolysis of estrone-sulfate (E1-S) and dehydroepiandrosterone-sulfate (DHEA-S), while sulfotransferases catalyze the reverse reaction and require 3-phosphoadenosine-5-phosphosulfate as a sulfate donor. These enzymes control the concentration of active estrogens and androgens in peripheral tissues. Aberant expression of STS and SULT genes has been found in both, benign hormone-dependent diseases and hormone-dependent cancers. The aim of this review is to present the current knowledge on the role of STS and SULT in gynecological cancers, endometrial (EC) and ovarian cancer (OC). EC is the most common and OC the most lethal gynecological cancer. These cancers primarily affect postmenopausal women and therefore rely on the local production of steroid hormones from inactive precursors, either DHEA-S or E1-S. Following cellular uptake by organic anion transporting polypeptides (OATP) or organic anion transporters (OAT), STS and SULT regulate the formation of active estrogens and androgens, thus disturbed balance between STS and SULT can contribute to the onset and progression of cancer. The importance of these enzymes in peripheral estrogen biosynthesis has long been recognized, and this review provides new data on the important role of STS and SULT in the formation and action of androgens, their regulation and inhibition, and their potential as prognostic biomarkers.
摘要:
硫酸酯酶(STS)和磺基转移酶(SULT)在类固醇激素的生物合成和作用中具有重要作用。STS催化硫酸雌酮(E1-S)和硫酸脱氢表雄酮(DHEA-S)的水解,而磺基转移酶催化逆反应,需要3-磷酸腺苷-5-磷酸硫酸盐作为硫酸盐供体。这些酶控制外周组织中活性雌激素和雄激素的浓度。在这两个基因中都发现了STS和SULT基因的异常表达,良性激素依赖性疾病和激素依赖性癌症。这篇综述的目的是介绍STS和SULT在妇科癌症中的作用,子宫内膜(EC)和卵巢癌(OC)。EC是最常见的,OC是最致命的妇科癌症。这些癌症主要影响绝经后妇女,因此依赖于非活性前体的类固醇激素的局部产生,DHEA-S或E1-S在有机阴离子转运多肽(OATP)或有机阴离子转运蛋白(OAT)的细胞摄取后,STS和SULT调节活性雌激素和雄激素的形成,因此,STS和SULT之间的平衡失调可能导致癌症的发生和进展。这些酶在外周雌激素生物合成中的重要性早已被认识到,这篇综述提供了关于STS和SULT在雄激素形成和作用中的重要作用的新数据,它们的调节和抑制,以及它们作为预后生物标志物的潜力。