Expression of Hypothalamic–Pituitary–Adrenal Axis in Common Skin Diseases: Evidence of its Association with Stress-related Disease Activity

Abstract

Hypothalamic-pituitary-adrenal (HPA) axis hormones and their receptors expressed in the skin are known to function locally, but how these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. We comprehensively reviewed the distribution and function of the central and peripheral HPA axis in various stress-related skin diseases. Previous studies have shown altered expression of central and peripheral HPA axis hormones in chronic inflammatory skin diseases and skin tumours, and that hyper-active lesional HPA axis hormones may negatively feedback to the central HPA axis and interact with some cytokines and neuropeptides, leading to symptom deterioration. This provides an evidence-based understanding of the expression of the central and peripheral HPA axis in common skin diseases and its association with disease activity.

Brain-Skin Connection: Stress, Inflammation and Skin Aging

“…The skin also developed a fully functional peripheral HPA system where CRH, ACTH, and their receptors are produced in skin cells [21, 22]. CRH is produced by epidermal and hair follicle keratinocytes, melanocytes, sebocytes, and mast cells upon stress, including immune cytokines, UV irradiation, and cutaneous pathology [23, 24].…”

Functional magnetic resonance imaging in dermatology: The skin, the brain and the invisible

“…Under normal circumstances HPA axis hormones contribute to skin homoeostasis, anti-inflammatory balance and antimicrobial defense. [6][7][8] However, under stress, the HPA axis may be altered resulting in proinflammatory hormonal effects, resistance of tissue receptors to glucocorticoids and mast cell activation in the skin. [6,9] In addition, a brain-derived nerve growth factor can mediate or enhance skin inflammation culminating in a "nervous breakdown of the skin," which manifests as a stress-induced exacerbation of an inflammatory skin disease.…”

“…[6][7][8] However, under stress, the HPA axis may be altered resulting in proinflammatory hormonal effects, resistance of tissue receptors to glucocorticoids and mast cell activation in the skin. [6,9] In addition, a brain-derived nerve growth factor can mediate or enhance skin inflammation culminating in a "nervous breakdown of the skin," which manifests as a stress-induced exacerbation of an inflammatory skin disease. [7,8,10] Indeed, there are numerous dermatological conditions strongly influenced by stress such as atopic eczema, psoriasis, pruritus or hyperhidrosis.…”

“…The skin has its own "peripheral" HPA axis to respond to stress and interact with the central HPA axis. [6,[25][26][27][28][29] Furthermore, the skin and brain age together as their intrinsic ageing strongly depends on a similar endocrine environment leading to the suggestion that skin ageing models represent an effective tool for understanding molecular ageing mechanisms of the brain. [30] The notion that skin may reflect a "diagnostic window into the brain" is tempting and the use of alpha-synuclein in skin nerve fibres biopsies to support diagnoses of Parkinson's disease [31,32] and fibroblast-based tests for Alzheimer's disease [33] is currently under investigation.…”

Dexamethasone Promotes Keratinocyte Proliferation by Triggering Keratinocyte Growth Factor in Mast Cells

“…It may also give feedback to the central system [18]. Moreover, recent findings that ACTH increases, but CRH decreases, the expression of the proinflammatory cytokine IL-18 in keratinocytes [20] provides another example of communication between the skin and the HPA axis. Indeed, psychosocial stressors that exceed an individual’s perceived ability to cope, trigger both central and peripheral pathways.…”