Production of 11-Oxygenated Androgens by Testicular Adrenal Rest Tumors.
Production of 11-Oxygenated Androgens by Testicular Adrenal Rest Tumors.
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通过睾丸肾上腺静脉肿瘤生产11-氧化的雄激素。
DOI：
10.1210/clinem/dgab598
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发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Claahsen-van der Grinten HL
中科院分区：
文献类型：
--
作者：
Schröder MAM;Turcu AF;O'Day P;van Herwaarden AE;Span PN;Auchus RJ;Sweep FCGJ;Claahsen-van der Grinten HL
睾丸肾上腺素瘤（TART）是典型21-羟化酶缺乏症（21OHD）男性的常见并发症。TART可能导致21OHD患者雄激素过量，但尚未对这些肿瘤的类固醇生成进行直接量化。我们旨在通过TART确定11-氧合19-碳（11oxC19）类固醇的生成。采用液相色谱-串联质谱法对7例21OHD和TART患者的左精索静脉（n = 7）和右精索静脉（n = 4）进行甾体激素检测，同时抽取外周血（n = 7）。为了比较，我们还测量了5名肾上腺切除术患者和12名年龄和bmi匹配的对照组的外周类固醇浓度。此外，在有和没有促肾上腺皮质激素（ACTH）刺激的TART细胞和肾上腺细胞条件培养基中对类固醇进行定量。与伴有TART的21OHD患者外周血相比，精索静脉样本显示11oxC19类固醇的11β-羟睾酮（11OHT， 96倍）梯度最高，其次是11-酮睾酮（47倍）和11β-羟雄烯二酮（11OHA4, 29倍），提示这些类固醇是在TART中产生的。与肾上腺细胞相比，ACTH刺激后的TART细胞产生更高水平的睾酮，A4和11OHA4水平较低，表明ACTH诱导了TART中睾酮的产生。在21OHD患者中，TART产生11oxC19类固醇，但比例与肾上腺不同。精子与外周静脉血液中11OHT的比例非常高，表明TART对睾酮的11-羟基化作用，体外实验结果表明这种代谢对acth敏感。
Testicular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen excess in 21OHD patients, but a direct quantification of steroidogenesis from these tumors has not been yet done. We aimed to define the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART. Using liquid chromatography-tandem mass spectrometry, steroids were measured in left (n = 7) and right (n = 4) spermatic vein and simultaneously drawn peripheral blood (n = 7) samples from 7 men with 21OHD and TART. For comparison, we also measured the peripheral steroid concentrations in 5 adrenalectomized patients and 12 age- and BMI-matched controls. Additionally, steroids were quantified in TART cell– and adrenal cell–conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation. Compared with peripheral blood from 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11β-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11β-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cells produced higher levels of testosterone and lower levels of A4 and 11OHA4 after ACTH stimulation compared with adrenal cells, indicating ACTH-induced production of testosterone in TART. In patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic vs peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in vitro results indicate that this metabolism is ACTH-sensitive.
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影响因子：
4.1
作者：
Storbeck, Karl-Heinz;Bloem, Liezl M.;Swart, Amanda C.
通讯作者：
Swart, Amanda C.
影响因子：
4.1
作者：
Auchus, Richard J.
通讯作者：
Auchus, Richard J.
影响因子：
5.8
作者：
COMBESMOUKHOVSKY, ME;KOTTLER, ML;ATTALI, JR
通讯作者：
ATTALI, JR
影响因子：
5.8
作者：
Imamichi, Yoshitaka;Yuhki, Koh-ichi;Yazawa, Takashi
通讯作者：
Yazawa, Takashi
DOI：
10.1016/j.jsbmb.2017.12.016
发表时间：
2018-04-01
影响因子：
4.1
作者：
Kamrath, Clemens;Wettstaedt, Lisa;Wudy, Stefan A.
通讯作者：
Wudy, Stefan A.