Mechanisms of exercise-induced alterations in the hypothalamo-pituitary adrenal axis activity

糖皮质激素是一种自然产生的荷尔蒙，在体内具有多种功能，包括控制血糖水平，动员脂肪和蛋白质储备，以及抑制免疫。在压力时期，下丘脑-垂体-肾上腺(HPA)轴释放高水平的糖皮质激素，为机体防御做好准备。然而，糖皮质激素的慢性升高是不可取的，似乎与许多免疫、生长、神经和代谢障碍有关。因此，糖皮质激素必须在体内通过大脑和脑下垂体中的特定糖皮质激素受体(即负反馈)以及各种靶组织(如脂肪、肌肉和肝脏)中的酶来严格调节，这些酶可以激活或灭活局部的糖皮质激素。糖皮质激素调节不良和HPA活性的慢性升高被认为是一种常见的临床疾病(胰岛素抵抗、高血糖、中心性肥胖和高血压)的关键，尽管其确切机制尚不清楚。矛盾的是，经常锻炼是HPA活性的有效激活剂，却有益于预防或改善许多此类代谢紊乱。我的实验室感兴趣的是确定定期运动(即训练)是否影响：1)基础HPA活性；2)HPA反馈敏感性；3)局部糖皮质激素激活。此外，我们特别感兴趣的是，定期锻炼对代谢综合征的一些预防作用是否通过HPA轴的变化来实现。我们最近发现，在健康的啮齿动物中，短期的运动行为会增加静息HPA的活动，而长期的训练会导致基础活动的减少。这些适应似乎是通过大脑和脑下垂体中关键调节蛋白基因表达的变化以及通过改变肾上腺对产生糖皮质激素的敏感性来调节的。我们现在感兴趣的是阐明中枢和外周HPA适应训练的分子机制，并探索运动、HPA活性和疾病预防之间的联系。

Glucocorticoids are naturally occurring hormones that have several functions within the body, which include control of blood sugar levels, mobilization of fat and protein stores and immune suppression. During periods of stress, the Hypothalamo-Pituitary-Adrenal (HPA) axis releases high levels of glucocorticoids that prepare the organism for defence. Chronic elevations in glucocorticoids are undesirable, however, and appear to be linked to a number of immune, growth, neurological and metabolic disorders. As such, glucocorticoids must be tightly regulated within the body via specific glucocorticoid receptors in the brain and pituitary gland (i.e. negative feedback) and by enzymes in the various target tissues (e.g. fat, muscle and liver) that can either activate or inactivate local glucocorticoids. Poor regulation of glucocorticoids and chronic elevations in HPA activity are thought to be critical in the development of a common clinical condition called the Metabolic Syndrome (insulin resistance, high blood glucose, central obesity and high blood pressure), although the exact mechanism for this is unclear. Paradoxically, regular exercise, which is a potent activator of the HPA activity, is beneficial in preventing or improving many of these metabolic disorders. My laboratory is interested in determining if regular exercise (i.e. training) influences: 1) basal HPA activity; 2) HPA feedback sensitivity and; 3) local glucocorticoid activation. Moreover, we are particularly interested if some of the preventative effects of regular exercise on the development of the Metabolic Syndrome are via alterations in the HPA axis. We have recently shown that short term exercise behaviour increases resting HPA activity, while long term training causes a reduction in basal activity in healthy rodents. These adaptations appear to be mediated by changes in the gene expression of key regulatory proteins in the brain and pituitary gland as well as by changing the adrenal gland sensitivity to produce glucocorticoids. We are now interested in elucidating the molecular mechanisms for central and peripheral HPA adaptation to training and to explore the links between exercise, HPA activity and disease prevention.