High-resolution daily profiles of tissue adrenal steroids by portable automated collection
High-resolution daily profiles of tissue adrenal steroids by portable automated collection
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通过便携式自动采集获得组织肾上腺类固醇的高分辨率每日概况
DOI：
10.1126/scitranslmed.adg8464
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发表时间：
2023
影响因子：
17.1
通讯作者：
Upton T
中科院分区：
文献类型：
--
作者：
Upton T
节律是内分泌系统固有的，这些激素振荡的破坏发生在疾病的早期阶段。由于肾上腺激素分泌的昼夜节律和超昼夜周期，传统的单时间点测量提供有限的信息节律性，关键是，不提供信息在睡眠期间，当许多激素波动从最低点到峰值浓度。如果在夜间尝试采血，那么这就需要进入临床研究单位，可能会有压力，并干扰睡眠。为了克服这个问题，并测量其靶组织内的游离激素，我们使用微透析，流动馏分收集器，液相色谱-串联质谱法，以获得高分辨率的配置文件，组织肾上腺皮质类固醇超过24小时，在214名健康志愿者。为了验证，我们在另外七名健康志愿者中比较了组织与血浆测量值。从皮下组织采集样本是安全的，耐受性良好，并允许大多数正常活动继续进行。除了皮质醇，我们确定了每日和ultradian变化游离可的松，皮质酮，18-羟基皮质醇，醛固酮，四氢皮质醇和别四氢皮质醇，和硫酸脱氢表雄酮的存在。我们使用数学和计算方法来量化激素在一天中不同时间的个体间变异性，并在按性别、年龄和体重指数分层的健康个体中开发正常的“动态标记”。我们的研究结果提供了对真实世界环境中组织中肾上腺类固醇动力学的深入了解，并可作为内分泌疾病生物标志物的规范性参考（ULTRADIAN，NCT 02934399）。
Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of the disease. Because adrenal hormones are secreted with both circadian and ultradian periods, conventional single–time point measurements provide limited information about rhythmicity and, crucially, do not provide information during sleep, when many hormones fluctuate from nadir to peak concentrations. If blood sampling is attempted overnight, then this necessitates admission to a clinical research unit, can be stressful, and disturbs sleep. To overcome this problem and to measure free hormones within their target tissues, we used microdialysis, an ambulatory fraction collector, and liquid chromatography–tandem mass spectrometry to obtain high-resolution profiles of tissue adrenal steroids over 24 hours in 214 healthy volunteers. For validation, we compared tissue against plasma measurements in a further seven healthy volunteers. Sample collection from subcutaneous tissue was safe, well tolerated, and allowed most normal activities to continue. In addition to cortisol, we identified daily and ultradian variation in free cortisone, corticosterone, 18-hydroxycortisol, aldosterone, tetrahydrocortisol and allo-tetrahydrocortisol, and the presence of dehydroepiandrosterone sulfate. We used mathematical and computational methods to quantify the interindividual variability of hormones at different times of the day and develop “dynamic markers” of normality in healthy individuals stratified by sex, age, and body mass index. Our results provide insight into the dynamics of adrenal steroids in tissue in real-world settings and may serve as a normative reference for biomarkers of endocrine disorders (ULTRADIAN, NCT02934399).
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正常男性和女性 24 小时内的 ACTH 和皮质醇脉动模式
影响因子：
3.2
作者：
P. Horrocks;A. F. Jones;W. Ratcliffe;G. Holder;Anne White;R. Holder;J. Ratcliffe;D. London
通讯作者：
D. London
影响因子：
3
作者：
Moškon M
通讯作者：
Moškon M
影响因子：
3.2
作者：
DAIDOH, H;MORITA, H;YASUDA, K
通讯作者：
YASUDA, K
影响因子：
7
作者：
S. Boker;Minquan Xu;Jennifer L. Rotondo;Kadijah King
通讯作者：
S. Boker;Minquan Xu;Jennifer L. Rotondo;Kadijah King
增加钾摄入量对肾上腺皮质和心血管对血管紧张素 II 反应的影响：随机交叉研究。
影响因子：
5.4
作者：
Dreier R;Andersen UB;Forman JL;Sheykhzade M;Egfjord M;Jeppesen JL
通讯作者：
Jeppesen JL