Endocrinology Unit, University/BHF Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Psychoneuroendocrinology. 2013 Aug;38(8):1271-80. doi: 10.1016/j.psyneuen.2012.11.010. Epub 2012 Dec 4.
Dysfunctional regulation of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an important biological mechanism underlying stress-related diseases; however, a better understanding of the interlinked neuroendocrine events driving the release of cortisol by this stress axis is essential for progress in preventing or halting irreversible development of adverse HPA-function. We aimed to investigate basal HPA-activity in a normal population in late adolescence, the time of life believed to overlap with HPA-axis maturation and establishment of a lasting set point level of HPA function. A total of 1258 participants (mean age 16.6 years) recruited from the Western Australian Pregnancy (Raine) Cohort provided fasting morning blood and saliva samples for basal HPA activity assessment. Irrespective of gender, linear regression modelling identified a positive correlation between the main components of the HPA-cascade of events, ACTH, total cortisol and free cortisol in saliva. Corticosteroid binding globulin (CBG) was inversely associated with free cortisol in saliva, an effect most clearly observed in boys. ACTH levels were lower, but cortisol levels were higher in girls than in boys. Girls may also be exposed to more bioactive cortisol, based on higher average free cortisol measured in saliva at awakening. These relatively higher female free cortisol levels were significantly reduced by oral contraceptive use, eliminating the gender specific difference in salivary cortisol. Free plasma cortisol, calculated from total circulating cortisol and CBG concentrations, was also significantly reduced in girls using oral contraceptives, possibly via an enhancing effect of oral contraceptives on blood CBG content. This study highlights a clear gender difference in HPA activity under non-stressful natural conditions. This finding may be relevant for research into sex-specific stress-related diseases with a typical onset in late adolescence.
下丘脑-垂体-肾上腺（HPA）轴的功能障碍调节被认为是与应激相关疾病相关的重要生物学机制；然而，更好地理解驱动该应激轴释放皮质醇的神经内分泌事件的相互联系对于预防或阻止不利的 HPA 功能的不可逆转发展至关重要。我们旨在研究青春期后期正常人群的基础 HPA 活性，这一时期被认为与 HPA 轴成熟和建立持久的 HPA 功能设定点水平重叠。总共招募了来自西澳大利亚妊娠（Raine）队列的 1258 名参与者（平均年龄 16.6 岁），他们提供了空腹晨血和唾液样本，以评估基础 HPA 活性。无论性别如何，线性回归模型都确定了 HPA 级联事件的主要成分，即促肾上腺皮质激素（ACTH）、总皮质醇和唾液中的游离皮质醇之间的正相关。皮质类固醇结合球蛋白（CBG）与唾液中的游离皮质醇呈负相关，这种效应在男孩中最为明显。女孩的 ACTH 水平较低，但皮质醇水平较高。女孩可能也暴露于更多的生物活性皮质醇，这基于在觉醒时唾液中测量的平均游离皮质醇更高。这些相对较高的女性游离皮质醇水平在使用口服避孕药的女性中显著降低，消除了唾液皮质醇的性别特异性差异。从总循环皮质醇和 CBG 浓度计算得出的游离血浆皮质醇在使用口服避孕药的女孩中也显著降低，这可能是由于口服避孕药对血液 CBG 含量的增强作用。本研究强调了在非应激自然条件下 HPA 活性的明显性别差异。这一发现可能与研究以青春期后期为典型发病期的与性别相关的应激相关疾病有关。
