Clinical significance of 11-oxygenated androgens.
Clinical significance of 11-oxygenated androgens.
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DOI：
10.1097/med.0000000000000334
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Auchus RJ
中科院分区：
文献类型：
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作者：
Turcu AF;Auchus RJ
肾上腺被认为是弱雄激素的来源，如脱氢表雄酮、硫酸脱氢表雄酮和雄烯二酮。新出现的证据表明，一组11-氧合19-碳（11oxC19）肾上腺衍生类固醇是临床上重要的雄激素。这类类固醇包括：11β-羟基雄烯二酮、11-酮雄烯二酮、11β-羟基睾酮和11-酮睾酮。本文将对11oxC19类固醇的合成、雄激素活性及其临床意义进行综述。11oxC19类固醇的临床相关性在于两个关键特征：1。所有11oxC19的合成主要来源于肾上腺皮质；和2。11-酮睾酮及其5α-还原代谢物11-酮二氢睾酮是人类雄激素受体的强效激动剂，分别类似于经典雄激素睾酮和二氢睾酮。最近的研究表明，21-羟化酶缺乏症和多囊卵巢综合征患者11oxC19类固醇的循环水平高于正常水平。11oxC19类固醇也被认为有助于去势抵抗性前列腺癌的进展。此外，11oxC19类固醇可能对肾上腺素亢进和绝经后妇女有临床意义。需要进一步的前瞻性研究来确定11oxC19类固醇在个体化患者护理中的临床应用。初步数据表明，这些生物标志物有望改善雄激素过量疾病的评估和管理。
The adrenal gland is considered a source of weak androgens, such as dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. Emerging evidence proposes a set of 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as clinically important androgens. Such steroids include: 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone. This review will discuss the synthesis, androgenic activity and clinical implications of the 11oxC19 steroids. The clinical relevance of the 11oxC19 steroids resides in two key characteristics: 1. the synthesis of all 11oxC19 originates predominantly in the adrenal cortex; and 2. 11-ketotestosterone and its 5α-reduced metabolite, 11-ketodihydrotestosterone are potent agonists of the human androgen receptor, similar to the classic androgens testosterone and dihydrotestosterone, respectively. Recent studies have demonstrated higher than normal circulating levels of 11oxC19 steroids in patients with 21-hydroxylase deficiency and in polycystic ovary syndrome. The 11oxC19 steroids are also thought to contribute to castration-resistant prostate cancer progression. Additionally, the 11oxC19 steroids might have clinical implications in adrenarche and postmenopausal women. Future prospective studies are needed to establish the clinical utility of the 11oxC19 steroids for individualized patient care. Preliminary data suggest that these biomarkers hold promise to improve the evaluation and management of androgen excess disorders.