Kelly Monica R, Yuen Fiona, Satterfield Brieann C, Auchus Richard J, Gaddameedhi Shobhan, Van Dongen Hans P A, Liu Peter Y
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
VA Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center, North Hills, CA, USA.
J Endocr Soc. 2022 Sep 29;6(12):bvac153. doi: 10.1210/jendso/bvac153. eCollection 2022 Oct 26.
Night-shift work causes circadian misalignment, predicts the development of metabolic diseases, and complicates the interpretation of hormone measurements.
To investigate endogenous circadian rhythms, dissociated from behavioral and environmental confounds, in adrenal and gonadal steroids after simulated shift work.
Fourteen healthy adults (ages 25.8 ± 3.2 years) were randomized to 3 days of night or day (control) shift work followed by a constant routine protocol designed to experimentally unveil rhythms driven endogenously by the central circadian pacemaker. Blood was sampled every 3 hours for 24 hours during the constant routine to concurrently obtain 16 Δ4 steroid profiles by mass spectrometry. Cosinor analyses of these profiles provided mesor (mean abundance), amplitude (oscillation magnitude), and acrophase (peak timing).
Night-shift work marginally increased cortisol by 1 μg/dL ( = 0.039), and inactive/weak derivatives cortisone ( = 0.003) and 18-hydroxycortisol ( < 0.001), but did not alter the mesor of potent androgens testosterone and 11-ketotestosterone. Adrenal-derived steroids, including 11-ketotestosterone ( < 0.01), showed robust circadian rhythmicity after either day- or night-shift work. In contrast, testosterone and progesterone showed no circadian pattern after both shift work conditions. Night-shift work did not alter the amplitude or acrophase of any of the steroid profiles.
Experimental circadian misalignment had minimal effects on steroidogenesis. Adrenal steroids, but not gonadal hormones, showed endogenous circadian regulation robust to prior shift schedule. This dichotomy may predispose night-shift workers to metabolic ill health. Furthermore, adrenal steroids, including cortisol and the main adrenal androgen 11-ketostosterone, should always be evaluated during the biological morning whereas assessment of gonadal steroids, particularly testosterone, is dependent on the shift-work schedule.
夜班工作会导致昼夜节律失调，预示着代谢性疾病的发展，并使激素测量结果的解读变得复杂。
研究模拟轮班工作后，肾上腺和性腺类固醇中与行为和环境混杂因素无关的内源性昼夜节律。
14名健康成年人（年龄25.8±3.2岁）被随机分配到3天的夜班或白班（对照）工作，然后进行持续常规方案，旨在通过实验揭示由中央昼夜节律起搏器内源性驱动的节律。在持续常规期间，每3小时采集一次血样，共采集24小时，通过质谱法同时获得16种Δ4类固醇谱。对这些谱进行余弦分析，得出中值（平均丰度）、振幅（振荡幅度）和峰值相位（峰值时间）。
夜班工作使皮质醇略微增加1μg/dL（P=0.039），使无活性/弱衍生物可的松（P=0.003）和18-羟皮质醇（P<0.001）增加，但并未改变强效雄激素睾酮和11-酮睾酮的中值。肾上腺衍生的类固醇，包括11-酮睾酮（P<0.01），在白班或夜班工作后均显示出强烈的昼夜节律性。相比之下，在两种轮班工作条件下，睾酮和孕酮均未显示出昼夜模式。夜班工作未改变任何类固醇谱的振幅或峰值相位。
实验性昼夜节律失调对类固醇生成的影响最小。肾上腺类固醇而非性腺激素显示出对内源性昼夜节律的调节作用，这种调节作用不受先前轮班时间表的影响。这种二分法可能使夜班工作者易患代谢性健康问题。此外，肾上腺类固醇，包括皮质醇和主要的肾上腺雄激素11-酮睾酮，应始终在生物早晨进行评估，而性腺类固醇，特别是睾酮的评估则取决于轮班工作时间表。
