Stress Hormone and Skin Disease

Stress activates several neural pathways. The main stress response systems are the locus coeruleus, sympathetic-adrenal medullary system, and the hypothalamic–pituitary–adrenal (HPA) axis (Zhang et al., 2005). Stressors stimulate the paraventricular nuclei of the hypothalamus, where corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are synthesized. CRH is a central component of the HPA axis and regulates the expression of pro-opiomelanocortin (POMC) and POMC-derived peptides (adrenocorticotropin (ACTH), ┙melanocyte-stimulating hormone (┙-MSH) and ┚-endorphin) from the anterior pituitary gland (Chrousos, 1998). CRH stimulates AVP secretion and AVP has synergistic effect with CRH, particularly under chronic stress. Pituitary ACTH stimulates adrenal cortisol and glucocorticoid production. Stress influences cellular and humoral immune responses by releasing glucocorticoid, catecholamine, and CRH and POMC peptide secretion as well as by altering cytokine profiles (Elenkov & Chrousos, 1999). The skin is directly exposed to various environmental stresses. Skin should be able to defense immediately against these stressors and reestablish tissue homeostasis. Recent studies have identified the existence of a peripheral stress response system equivalent to the central HPA axis in the skin. CRH, urocortin, POMC-derived peptides, and their receptors are expressed in normal skin. Response to local CRH stimulation in melanoncytes and fibroblasts confirmed the presence of a fully functional local HPA axis (Slominski et al., 2007). Stress hormone of the HPA axis produced locally under stress enables the skin to regulate the local homeostasis. CRH, the main coordinator of the stress response can be secreted by various skin cells including epidermal and hair follicle keratinocytes, sebocytes and mast cells (Kono et al., 2001). The peptide acts through CRH receptor (CRH-R), which belong to the calcitonin/vasoactive intestinal peptide (VIP)/growth hormone-releasing hormone subfamily of G protein-coupled receptors. These include CRH-R1 and CRH-R2, both being subdivided into CRH-R1┙/1┚ and CRH-R2┙/2┚. CRH-R1 is the major receptor in the epidermis and dermis. CRH-R2 is the predominant type of receptor in adnexal structures (Chalmers et al., 1996; Pisarchik & Slominski, 2004; Slominski et al., 2001). CRH has a pleiotropic effect in the skin depending on the cell type and experimental growth conditions. CRH stimulates diverse signaling pathways via CRH-R1 activation, which modulates proliferation, differentiation, apoptosis and proor anti-inflammatory activities of skin cells (Elenkov & Chrousos, 1999; O’Kane et al., 2006). CRH activates various cells to release the pro-inflammatory cytokines. For example, CRH stimulates interleukin (IL)-6 release by keratinocytes (Zbytek et al., 2002) and IL-1┚ release by monocytes (Paez Pereda et al., 1995). Skin mast cells function as “sensors” of environmental and emotional stress (Theoharides et al., 2010). There have been a few