The adrenal gland has traditionally been viewed as a source of "weak androgens"; however, emerging evidence indicates 11-oxy-androgens of adrenal origin are metabolized in peripheral tissues to potent androgens. Also emerging is the role of gut bacteria in the conversion of C21 glucocorticoids to 11-oxygenated C19 androgens. Clostridium scindens ATCC 35,704 is a gut microbe capable of converting cortisol into 11-oxy-androgens by cleaving the side-chain. The desA and desB genes encode steroid-17,20-desmolase. Our prior study indicated that the urinary tract bacterium, Propionimicrobium lymphophilum ACS-093-V-SCH5 encodes desAB and converts cortisol to 11β-hydroxyandrostenedione. We wanted to determine how widespread this function occurs in the human microbiome. Phylogenetic and sequence similarity network analyses indicated that the steroid-17,20-desmolase pathway is taxonomically rare and located in gut and urogenital microbiomes. Two microbes from each of these niches, C. scindens and Propionimicrobium lymphophilum, respectively, were screened for activity against endogenous (cortisol, cortisone, and allotetrahydrocortisol) and exogenous (prednisone, prednisolone, dexamethasone, and 9-fluorocortisol) glucocorticoids. LC/MS analysis showed that both microbes were able to side-chain cleave all glucocorticoids, forming 11-oxy-androgens. Pure recombinant DesAB from C. scindens showed the highest activity against prednisone, a commonly prescribed glucocorticoid. In addition, 0.1 nM 1,4-androstadiene-3,11,17-trione, bacterial side-chain cleavage product of prednisone, showed significant proliferation relative to vehicle in androgen-dependent growth LNCaP prostate cancer cells after 24 h (2.3 fold; P <  0.01) and 72 h (1.6 fold; P < 0.01). Taken together, DesAB-expressing microbes may be an overlooked source of androgens in the body, potentially contributing to various disease states, such as prostate cancer.

中文翻译：

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细菌类固醇17,20-脱模酶是一种分类学上罕见的酶促途径，可将泼尼松转化为1,4-雄烷二烯3,11,17-三酮，一种可引起前列腺癌细胞增殖的代谢物。

肾上腺传统上被视为“弱雄激素”的来源。然而，新的证据表明，肾上腺来源的11-氧基-雄激素在周围组织中被代谢为有效的雄激素。还出现了肠道细菌在将C21糖皮质激素转化为11-氧化的C19雄激素中的作用。梭菌梭状芽胞杆菌ATCC 35,704是一种能够通过裂解侧链将皮质醇转化为11-氧基-雄激素的肠道微生物。desA和desB基因编码类固醇17,20-脱摩尔酶。我们先前的研究表明，尿道细菌丙酸丙酸杆菌ACS-093-V-SCH5编码desAB，并将皮质醇转化为11β-羟基雄烯二酮。我们想确定这种功能在人类微生物组中的分布程度。系统发育和序列相似性网络分析表明，类固醇17,20-脱粘酶途径在分类学上是罕见的，位于肠道和泌尿生殖器微生物区系中。分别筛选了来自这些小生境中的两个微生物，即梭状梭菌和丙酸丙酸杆菌，针对内源性（皮质醇，可的松和异四氢皮质醇）和外源性（泼尼松，泼尼松龙，地塞米松和9-氟皮质醇）糖皮质激素的活性。LC / MS分析表明，两种微生物都能够侧链裂解所有糖皮质激素，形成11-氧基-雄激素。来自梭菌的纯重组DesAB对强的松（通常处方的糖皮质激素）表现出最高的活性。此外，泼尼松的细菌侧链裂解产物0.1 nM 1,4-雄甾二烯-3,11,17-三酮，在雄激素依赖性生长的LNCaP前列腺癌细胞中，在24小时（2.3倍； P <0.01）和72小时（1.6倍； P <0.01）后，相对于赋形剂显示出显着的增殖。两者合计，表达DesAB的微生物可能是体内雄激素的一个被忽视的来源，可能导致多种疾病，例如前列腺癌。