11-Oxygenated C19 Steroids Do Not Decline With Age in Women
11-Oxygenated C19 Steroids Do Not Decline With Age in Women
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DOI：
10.1210/jc.2018-02527
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发表时间：
2019-07-01
影响因子：
5.8
通讯作者：
Turcu, Adina F.
中科院分区：
文献类型：
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作者：
Nanba, Aya T.;Rege, Juilee;Turcu, Adina F.
背景：卵巢和肾上腺是女性体内雄激素的来源。尽管脱氢表雄酮（DHEA）、硫酸脱氢表雄酮（DHEAS）和睾酮(T)都随着年龄的增长而下降，但这些C-19类固醇与绝经后妇女雄激素作用的参数相关性很差。目的：综合比较绝经前和绝经后妇女的雄激素水平。方法：对19种甾体进行定量分析，包括脱氢表雄酮；脱氢表雄酮;T;雄烯二酮(A4);以及以下肾上腺特异性11-氧合C-19类固醇（11 -氧雄激素）：11-羟基睾酮（11OHT）， 11-酮睾酮（11KT）， 11-羟基雄烯二酮（11OHA4）和11-酮雄烯二酮(11KA4)-使用液相色谱-串联质谱法从100名绝经前（20至40岁）和100名绝经后（年龄>= 60岁）妇女的早晨血清中提取。采用细胞色素b(5) （CYB5A）或硫转移酶2A1 （SULT2A1）对8名绝经前和绝经后妇女的正常肾上腺进行了3 -羟基类固醇脱氢酶2型（HSD3B2）的双免疫荧光检测。结果：绝经前妇女DHEA、DHEAS、A4和T显著高于绝经后妇女（分别为2.9倍、2.8倍、2.9倍和1.6倍；P < 0.0001）。11-氧雄激素不随年龄增长而下降，11OHT/T、11OHA4/A4与年龄呈显著正相关（r分别为0.5、0.8,P < 0.0001）。双免疫荧光分析显示，随着老年肾上腺网状带的退化，HSD3B2和CYB5A明显的区隔性减弱，HSD3B2和CYB5A区域出现重叠。结论：与DHEA、DHEAS、A4和T不同，11氧雄激素在老年妇女中不会下降。肾上腺皮质的结构变化可能解释了老年女性雄激素谱的演变。
Context: The ovaries and adrenals are sources of androgens in women. Although dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and testosterone (T) all decline with age, these C-19 steroids correlate poorly with parameters of androgen action in postmenopausal women.Objective: To comprehensively compare the androgen profiles of pre-and postmenopausal women.Methods: We quantified 19 steroids-including DHEA; DHEAS; T; androstenedione (A4); and the following adrenal-specific 11-oxygenated C-19 steroids (11oxyandrogens): 11 beta-hydroxytestosterone (11OHT), 11-ketotestosterone (11KT), 11 beta-hydroxyandrostenedione (11OHA4), and 11-ketoandrostenedione (11KA4)-using liquid chromatography-tandem mass spectrometry in morning serum obtained from 100 premenopausal (age 20 to 40 years) and 100 postmenopausal (age >= 60 years) women. Double immunofluorescence of 3 beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) with cytochrome b(5) (CYB5A) or sulfotransferase 2A1 (SULT2A1) was performed in normal adrenal glands obtained from eight premenopausal and eight postmenopausal women.Results: DHEA, DHEAS, A4, and T were significantly higher in pre- than in postmenopausal women (2.9, 2.8, 2.9, and 1.6-fold, respectively; P < 0.0001). In contrast, the 11-oxyandrogens did not decrease with aging, and the 11OHT/T and 11OHA4/A4 ratios showed strong positive correlations with age (r = 0.5 and 0.8, respectively; P < 0.0001). Double immunofluorescence analysis showed that with the involution of the zona reticularis in the old adrenals, the sharp zonal segregation of HSD3B2 and CYB5A becomes less distinct, and areas of HSD3B2 and CYB5A overlap are observed.Conclusions: Unlike DHEA, DHEAS, A4, and T, the 11oxyandrogens do not decline in aging women. Structural changes within the adrenal cortex might explain the evolution of androgen profiles in aging women.