Cariello Marica, Ducheix Simon, Maqdasy Salwan, Baron Silvère, Moschetta Antonio, Lobaccaro Jean-Marc A
"Aldo Moro" University of Bari, Italy.
Istituto Nazionale Biostrutture e Biosistemi, Roma, Italy.
Nucl Recept Signal. 2018 Oct 16;15:1550762918801070. doi: 10.1177/1550762918801070. eCollection 2018.
Androgens and androgen receptor (AR, NR3C4) clearly play a crucial role in prostate cancer progression. Besides, the link between metabolic disorders and the risk of developing a prostate cancer has been emerging these last years. Interestingly, "lipid" nuclear receptors such as LXRα/NR1H3 and LXRβ/NR1H2 (as well as FXRα/NR1H4 and SHP/NR0B2) have been described to decrease the lipid metabolism, while AR increases it. Moreover, these former orphan nuclear receptors can regulate androgen levels and modulate AR activity. Thus, it is not surprising to find such receptors involved in the physiology of prostate. This review is focused on the roles of liver X receptors (LXRs), farnesoid X receptor (FXR), and small heterodimeric partner (SHP) in prostate physiology and their capabilities to interfere with the androgen-regulated pathways by modulating the levels of active androgen within the prostate. By the use of prostate cancer cell lines, mice deficient for these nuclear receptors and human tissue libraries, several authors have pointed out the putative possibility to pharmacologically target these receptors. These data open a new field of research for the development of new drugs that could overcome the castration resistance in prostate cancer, a usual phenomenon in patients.
雄激素和雄激素受体（AR，NR3C4）在前列腺癌进展中显然起着关键作用。此外，近年来，代谢紊乱与患前列腺癌风险之间的联系日益显现。有趣的是，诸如肝X受体α（LXRα/NR1H3）和肝X受体β（LXRβ/NR1H2）（以及法尼醇X受体α（FXRα/NR1H4）和小异二聚体伴侣蛋白（SHP/NR0B2））等“脂质”核受体已被描述为可降低脂质代谢，而AR则会增加脂质代谢。此外，这些以前的孤儿核受体可以调节雄激素水平并调节AR活性。因此，发现此类受体参与前列腺生理过程也就不足为奇了。本综述聚焦于肝X受体（LXRs）、法尼醇X受体（FXR）和小异二聚体伴侣蛋白（SHP）在前列腺生理中的作用，以及它们通过调节前列腺内活性雄激素水平来干扰雄激素调节途径的能力。通过使用前列腺癌细胞系、缺乏这些核受体的小鼠和人类组织文库，几位作者指出了对这些受体进行药物靶向治疗的潜在可能性。这些数据为开发能够克服前列腺癌去势抵抗（这在患者中是一种常见现象）的新药开辟了一个新的研究领域。
