Gunn Pippa J, Middleton Benita, Davies Sarah K, Revell Victoria L, Skene Debra J
a Chronobiology, Faculty of Health and Medical Sciences , University of Surrey , Guildford , United Kingdom.
b Radcliffe Department of Medicine, University of Oxford, Level 6 , West Wing, John Radcliffe Hospital , Headington , Oxford , United Kingdom.
Chronobiol Int. 2016;33(1):39-50. doi: 10.3109/07420528.2015.1112396. Epub 2016 Jan 5.
Conflicting evidence exists as to whether there are differences between males and females in circadian timing. The aim of the current study was to assess whether sex differences are present in the circadian regulation of melatonin and cortisol in plasma and urine matrices during a constant routine protocol. Thirty-two healthy individuals (16 females taking the oral contraceptive pill (OCP)), aged 23.8 ± 3.7 (mean ± SD) years, participated. Blood (hourly) and urine (4-hourly) samples were collected for measurement of plasma melatonin and cortisol, and urinary 6-sulfatoxymelatonin (aMT6s) and cortisol, respectively. Data from 28 individuals (14 females) showed no significant differences in the timing of plasma and urinary circadian phase markers between sexes. Females, however, exhibited significantly greater levels of plasma melatonin and cortisol than males (AUC melatonin: 937 ± 104 (mean ± SEM) vs. 642 ± 47 pg/ml.h; AUC cortisol: 13581 ± 1313 vs. 7340 ± 368 mmol/L.h). Females also exhibited a significantly higher amplitude rhythm in both hormones (melatonin: 43.8 ± 5.8 vs. 29.9 ± 2.3 pg/ml; cortisol: 241.7 ± 23.1 vs. 161.8 ± 15.9 mmol/L). Males excreted significantly more urinary cortisol than females during the CR (519.5 ± 63.8 vs. 349.2 ± 39.3 mol) but aMT6s levels did not differ between sexes. It was not possible to distinguish whether the elevated plasma melatonin and cortisol levels observed in females resulted from innate sex differences or the OCP affecting the synthetic and metabolic pathways of these hormones. The fact that the sex differences observed in total plasma concentrations for melatonin and cortisol were not reproduced in the urinary markers challenges their use as a proxy for plasma levels in circadian research, especially in OCP users.
关于昼夜节律在男性和女性之间是否存在差异，存在相互矛盾的证据。本研究的目的是评估在持续日常方案期间，血浆和尿液基质中褪黑素和皮质醇的昼夜调节是否存在性别差异。32名年龄为23.8±3.7（均值±标准差）岁的健康个体（16名服用口服避孕药（OCP）的女性）参与了研究。分别每小时采集血液样本、每4小时采集尿液样本，用于测量血浆褪黑素和皮质醇、尿6-硫酸氧基褪黑素（aMT6s）和皮质醇。来自28名个体（14名女性）的数据显示，性别之间血浆和尿液昼夜节律相位标志物的时间没有显著差异。然而，女性的血浆褪黑素和皮质醇水平显著高于男性（褪黑素曲线下面积：937±104（均值±标准误）vs. 642±47 pg/ml·h；皮质醇曲线下面积：13581±1313 vs. 7340±368 mmol/L·h）。女性在这两种激素中也表现出显著更高的振幅节律（褪黑素：43.8±5.8 vs. 29.9±2.3 pg/ml；皮质醇：241.7±23.1 vs. 161.8±15.9 mmol/L）。在持续日常方案期间，男性排泄的尿皮质醇显著多于女性（519.5±63.8 vs. 349.2±39.3 μmol），但aMT6s水平在性别之间没有差异。无法区分女性中观察到的血浆褪黑素和皮质醇水平升高是源于先天性别差异还是OCP影响了这些激素的合成和代谢途径。在尿液标志物中未重现血浆褪黑素和皮质醇总浓度中观察到的性别差异这一事实，对它们在昼夜节律研究中作为血浆水平替代指标的用途提出了挑战，尤其是在OCP使用者中。
