Pretorius Elzette, Arlt Wiebke, Storbeck Karl-Heinz
Department of Biochemistry, Stellenbosch University, Stellenbosch, 7600, South Africa.
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, UK.
Mol Cell Endocrinol. 2017 Feb 5;441:76-85. doi: 10.1016/j.mce.2016.08.014. Epub 2016 Aug 9.
The abundant adrenal C19 steroid 11β-hydroxyandrostenedione (11OHA4) has been written off as a dead-end product of adrenal steroidogenesis. However, recent evidence has demonstrated that 11OHA4 is the precursor to the potent androgenic 11-oxygenated steroids, 11-ketotestosterone and 11-ketodihydrotestosterone, that bind and activate the human androgen receptor similarly to testosterone and DHT. The significance of this discovery becomes apparent when considering androgen dependent diseases such as castration resistant prostate cancer and diseases associated with androgen excess, e.g. congenital adrenal hyperplasia and polycystic ovary syndrome. In this review we describe the production and metabolism of 11-oxygenated steroids. We subsequently discuss their androgenic activity and highlight the putative role of these androgens in disease states.
肾上腺中丰富的C19类固醇11β-羟基雄烯二酮（11OHA4）一直被视为肾上腺类固醇生成的终末产物。然而，最近有证据表明，11OHA4是强效雄激素性11-氧化类固醇（11-酮睾酮和11-酮双氢睾酮）的前体，这些类固醇与睾酮和双氢睾酮类似，能结合并激活人类雄激素受体。当考虑到雄激素依赖性疾病，如去势抵抗性前列腺癌以及与雄激素过多相关的疾病，如先天性肾上腺增生症和多囊卵巢综合征时，这一发现的重要性就变得显而易见。在本综述中，我们描述了11-氧化类固醇的产生和代谢。随后，我们讨论它们的雄激素活性，并强调这些雄激素在疾病状态中的假定作用。
