Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA.
Steroids. 2010 Jul;75(7):467-76. doi: 10.1016/j.steroids.2010.02.004. Epub 2010 Feb 13.
Steroid hormones participate in organ development, reproduction, body homeostasis, and stress responses. The steroid machinery is expressed in a development- and tissue-specific manner, with the expression of these factors being tightly regulated by an array of transcription factors (TFs). Epigenetics provides an additional layer of gene regulation through DNA methylation and histone tail modifications. Evidence of epigenetic regulation of key steroidogenic enzymes is increasing, though this does not seem to be a predominant regulatory pathway. Steroid hormones exert their action in target tissues through steroid nuclear receptors belonging to the NR3A and NR3C families. Nuclear receptor expression levels and post-translational modifications regulate their function and dictate their sensitivity to steroid ligands. Nuclear receptors and TFs are more likely to be epigenetically regulated than proteins involved in steroidogenesis and have secondary impact on the expression of these steroidogenic enzymes. Here we review evidence for epigenetic regulation of enzymes, transcription factors, and nuclear receptors related to steroid biogenesis and action.
甾体激素参与器官发育、生殖、体内平衡和应激反应。甾体机制以发育和组织特异性的方式表达,这些因素的表达受到一系列转录因子 (TF) 的严格调控。表观遗传学通过 DNA 甲基化和组蛋白尾部修饰提供了基因调控的附加层。越来越多的证据表明关键的甾体生成酶受到表观遗传调控,尽管这似乎不是主要的调控途径。甾体激素通过属于 NR3A 和 NR3C 家族的甾体核受体在靶组织中发挥作用。核受体表达水平和翻译后修饰调节其功能,并决定其对甾体配体的敏感性。核受体和 TF 比参与甾体生成的蛋白更有可能受到表观遗传调控,并对这些甾体生成酶的表达产生次要影响。在这里,我们回顾了与甾体生物合成和作用相关的酶、转录因子和核受体的表观遗传调控的证据。