Kinlein Scott A, Shahanoor Ziasmin, Romeo Russell D, Karatsoreos Ilia N
Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington 99164.
Department of Psychology and Neuroscience and Behavior Program, Barnard College of Columbia University, New York, New York 10027.
Endocrinology. 2017 Jul 1;158(7):2239-2254. doi: 10.1210/en.2017-00208.
Glucocorticoids are potent modulators of metabolic and behavioral function. Their role as mediators in the "stress response" is well known, but arguably their primary physiological function is in the regulation of cellular and organismal metabolism. Disruption of normal glucocorticoid function is linked to metabolic disease, such as Cushing syndrome. Glucocorticoids are also elevated in many forms of obesity, suggesting that there are bidirectional effects of these potent hormones on metabolism and metabolic function. Adolescence is a time of rapid physical growth, and disruptions during this critical time likely have important implications for adult function. The hypothalamic-pituitary-adrenal axis continues to mature during this period, as do tissues that respond to glucocorticoids. In this work, we investigate how chronic noninvasive exposure to corticosterone affects metabolic outcomes (body weight, body composition, insulin, and glucose homeostasis), as well as changes in bone density in both adult and adolescent male mice. Specifically, we report a different pattern of metabolic effects in adolescent mice compared with adults, as well as an altered trajectory of recovery in adolescents and adults. Together, these data indicate the profound influence that adolescent development has on the metabolic outcomes of chronic corticosterone exposure, and describe a tractable model for understanding the short- and long-term impacts of hypercortisolemic states on physiological and neurobehavioral functions.
糖皮质激素是代谢和行为功能的强效调节因子。它们作为“应激反应”介质的作用众所周知，但可以说它们的主要生理功能是调节细胞和机体代谢。正常糖皮质激素功能的破坏与代谢疾病有关，如库欣综合征。在多种形式的肥胖中糖皮质激素水平也会升高，这表明这些强效激素对代谢和代谢功能存在双向影响。青春期是身体快速生长的时期，在这个关键时期出现的功能紊乱可能对成年后的功能产生重要影响。在此期间，下丘脑 - 垂体 - 肾上腺轴持续成熟，对糖皮质激素产生反应的组织也是如此。在这项研究中，我们调查了成年和青春期雄性小鼠长期非侵入性暴露于皮质酮如何影响代谢结果（体重、身体组成、胰岛素和葡萄糖稳态）以及骨密度变化。具体而言，我们报告了与成年小鼠相比青春期小鼠不同的代谢效应模式，以及青春期和成年小鼠恢复轨迹的改变。这些数据共同表明青春期发育对长期暴露于皮质酮的代谢结果具有深远影响，并描述了一个易于处理的模型，用于理解高皮质醇血症状态对生理和神经行为功能的短期和长期影响。
