Cutaneous hypothalamic-pituitary-adrenal axis homolog: regulation by ultraviolet radiation

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis maintains basal and stress-related homeostasis in vertebrates. Skin expresses all elements of the HPA axis including corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), ACTH, β-endorphin (β-END) with corresponding receptors, the glucocorticoidogenic pathway, and the glucocorticoid receptor (GR). To test the hypothesis that cutaneous responses to environmental stressors follow the organizational structure of the central response to stress, the activity of the “cutaneous HPA” axis homolog was investigated after exposure to ultraviolet radiation (UVR) wavelengths of UVA (320–400 nm), UVB (280–320 nm), and UVC (100–280 nm) in human skin organ culture and in co-cultured keratinocytes/melanocytes. The level of stimulation of CRH, POMC, MC1R, MC2R, CYP11A1, and CYP11B1 genes was dependent on UV wavelengths and doses, with the highest effects observed for highly energetic UVC and UVB. ELISA and Western assays showed significant production of CRH, POMC, ACTH, and CYP11A1 proteins and of cortisol, with a decrease in GR expression only after UVB and UVC. However, β-END expression was also stimulated by UVA. Immunocytochemistry localized the deposition of the aforesaid antigens predominantly to the epidermis with additional accumulation of CRH, β-END, and ACTH in the dermis. UVR-stimulated CYP11A1 expression was seen in the basal layer of the epidermis and cells of adjacent dermis. Thus, the capacity to activate or change the spatial distribution of the cutaneous HPA axis elements is dependent on highly energetic wavelengths (UVC and UVB), implying a dependence of a local stress response on their noxious activity with overlapping or alternative mechanisms activated by UVA.

Non-breeding feather concentrations of testosterone, corticosterone and cortisol are associated with subsequent survival in wild house sparrows

“…Local GC synthesis occurs in mammalian skin and hair follicles, and human skin cells can synthesize both cortisol and corticosterone [44,45]. Local cortisol synthesis in skin could thereby be dissociated from adrenal corticosterone synthesis and might reflect an independent fitness-related trait, such as the ability to heal from injuries, cope with ectoparasites, or the extent of ultraviolet light exposure [46].…”

Skin β-Endorphin Mediates Addiction to UV Light

“…POMC is post-translationally cleaved into biologically active peptides, one of which is α-Melanocyte Stimulating Hormone (MSH) that mediates the tanning process by stimulating adjacent melanocytes to produce the brown/black pigment eumelanin (D'Orazio et al, 2006). The endogenous opioid β-endorphin is also post-translationally generated in skin by cleavage of the POMC pro-peptide in response to UV radiation (Cui et al, 2007; Skobowiat et al, 2011; Slominski and Wortsman, 2000). β-endorphin is the most abundant endogenous opioid, with basal plasma levels of 1pM-12pM (Bender et al, 2007; Fassoulaki et al, 2007; Leppaluoto et al, 2008), and intravenous administration of β-endorphin has been shown to cause analgesia, (Tseng et al, 1976).…”

Interleukin 10 protects primary melanocyte by activation of Stat-3 and PI3K/Akt/NF-κB signaling pathways

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