Chrousos G P
Pediatric Endocrinology Section, PREB, NICHD, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Obes Relat Metab Disord. 2000 Jun;24 Suppl 2:S50-5. doi: 10.1038/sj.ijo.0801278.
The stress system coordinates the adaptive response of the organism to real or perceived stressors. The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine/ autonomic (LC/NE) systems and their peripheral effectors, the hypothalamic-pituitary-adrenal (HPA) axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. Thus, CRH and the LC/NE system stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the amygdala, which are responsible for the generation of fear. Hypothalamic CRH plays an important role in inhibiting gonadotropin-releasing hormone secretion during stress, while via somatostatin it also inhibits growth hormone, thyrotropin-releasing hormone and thyrotropin secretion, suppressing thus reproduction, growth and thyroid function. Glucocorticoids directly inhibit pituitary gonadotropin, growth hormone and thyrotropin secretion and make the target tissues of sex steroids and growth factors resistant to these substances. In addition, glucocorticoids stimulate hepatic gluconeogenesis, and inhibit or potentiate insulin actions on skeletal muscle and adipose tissue respectively, ultimately promoting visceral adiposity and the metabolic syndrome. Glucocorticoids also have direct effects on the bone, inhibiting osteoblastic activity and causing osteoporosis. Obese subjects with psychiatric manifestations ranging from those of melancholic depression to anxiety with perception of 'uncontrollable' stress, frequently have mild hypercortisolism, while carefully screened obese subjects with no such manifestations are eucortisolemic. The former may have stress-induced glucocorticoid-mediated visceral obesity and metabolic syndrome manifestations, which in the extreme may be called a pseudo-Cushing state that needs to be differentiated from frank Cushing syndrome. Stress-induced hypercortisolism and visceral obesity and their cardiovascular and other sequelae increase the all-cause mortality risk of affected subjects by 2-3-fold and curtail their life expectancy by several years.
应激系统协调机体对实际或感知到的应激源的适应性反应。应激系统的主要组成部分是促肾上腺皮质激素释放激素（CRH）和蓝斑 - 去甲肾上腺素/自主神经系统（LC/NE）及其外周效应器、下丘脑 - 垂体 - 肾上腺（HPA）轴以及自主神经系统的分支。应激系统的激活会导致行为和外周变化，从而提高机体调节内环境稳定的能力并增加其生存机会。因此，CRH和LC/NE系统会刺激觉醒和注意力，以及参与预期和奖励现象的中脑皮质边缘多巴胺能系统，还有负责产生恐惧的杏仁核。下丘脑CRH在应激期间抑制促性腺激素释放激素分泌方面发挥重要作用，同时通过生长抑素它还抑制生长激素、促甲状腺激素释放激素和促甲状腺激素分泌，从而抑制生殖、生长和甲状腺功能。糖皮质激素直接抑制垂体促性腺激素、生长激素和促甲状腺激素分泌，并使性类固醇和生长因子的靶组织对这些物质产生抗性。此外，糖皮质激素刺激肝脏糖异生，并分别抑制或增强胰岛素对骨骼肌和脂肪组织的作用，最终促进内脏肥胖和代谢综合征。糖皮质激素还对骨骼有直接影响，抑制成骨细胞活性并导致骨质疏松症。有从忧郁症到伴有“无法控制”应激感知的焦虑等精神症状的肥胖受试者，常常有轻度皮质醇增多症，而经过仔细筛查没有此类症状的肥胖受试者则皮质醇水平正常。前者可能有应激诱导的糖皮质激素介导的内脏肥胖和代谢综合征表现，在极端情况下可能被称为假性库欣状态，需要与真性库欣综合征相鉴别。应激诱导的皮质醇增多症和内脏肥胖及其心血管和其他后遗症使受影响受试者的全因死亡风险增加2至3倍，并使其预期寿命缩短数年。
