Turcu Adina F, Auchus Richard J
aDivision of Metabolism, Endocrinology and Diabetes bDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
Curr Opin Endocrinol Diabetes Obes. 2017 Jun;24(3):252-259. doi: 10.1097/MED.0000000000000334.
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. The present 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: the synthesis of all 11oxC19 originates predominantly in the adrenal cortex, and 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. In addition, 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.
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。新出现的证据提出了一组11-氧化-19碳（11oxC19）肾上腺衍生类固醇作为具有临床重要性的雄激素。这类类固醇包括11β-羟基雄烯二酮、11-酮基雄烯二酮、11β-羟基睾酮和11-酮基睾酮。本综述将讨论11oxC19类固醇的合成、雄激素活性及临床意义。
11oxC19类固醇的临床相关性在于两个关键特征：所有11oxC19类固醇的合成主要起源于肾上腺皮质，且11-酮基睾酮及其5α-还原代谢产物11-酮基二氢睾酮分别是人类雄激素受体的强效激动剂，类似于经典雄激素睾酮和二氢睾酮。最近的研究表明，21-羟化酶缺乏症患者和多囊卵巢综合征患者的11oxC19类固醇循环水平高于正常。11oxC19类固醇也被认为与去势抵抗性前列腺癌进展有关。此外，11oxC19类固醇可能对肾上腺初现和绝经后女性具有临床意义。
需要未来的前瞻性研究来确立11oxC19类固醇在个体化患者护理中的临床效用。初步数据表明，这些生物标志物有望改善雄激素过多症的评估和管理。
