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.
About this article
Cite this article
Chrousos, G. The role of stress and the hypothalamic–pituitary–adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes. Int J Obes 24, S50–S55 (2000). https://doi.org/10.1038/sj.ijo.0801278
- Cushing's syndrome
Improvements to Healthspan Through Environmental Enrichment and Lifestyle Interventions: Where Are We Now?
Frontiers in Neuroscience (2020)
Emotional distress, brain functioning, and biobehavioral processes in cancer patients: a neuroimaging review and future directions
CNS Spectrums (2020)
Cardiorenal metabolic biomarkers link early life stress to risk of non-communicable diseases and adverse mental health outcomes
Scientific Reports (2020)
Nanoplastics impact the zebrafish (Danio rerio) transcriptome: Associated developmental and neurobehavioral consequences
Environmental Pollution (2020)
The combined effect of socioeconomic status and metabolic syndrome on depression: the Korean National Health and Nutrition Examination Survey (KNHANES)
BMC Public Health (2020)