Table 1.

Major Stress Mediators in Skin

Stress Mediator	Source	Effector Cell	Functions in Skin
CRH	Hypothalamus; Skin keratinocytes, sebacytes, and mast cells	CRH-R1 is expressed in epidermis, dermis and subcutis layer; CRH-R2 is expressed in in hair follicle keratinocytes and papilla fibroblasts	Stimulation of downstream ACTH and cortisol production; Proliferation, differentiation, apoptosis, inflammation, and angiogenesis.
ACTH	Pituitary gland; Skin melanocytes, epidermal and hair follicle keratinocytes and dermal fibroblasts; Langerhan cells, monocytes, and macrophages	MC2-R is expressed in skin melanocytes, hair follicles, epidermal keratinocytes, sebaceous and eccrine glands, as well as dermal fibroblasts, sebaceous and eccrine glands, muscle and dermal blood vessels	Stimulation of cortisol and cortocosterone production; Melanogenesis, cytokine production, cell proliferation, dendritic formation, hair growth, immune and inflammation regulation.
Cortisol	Adrenal cortex; Skin hair follicles, melanocytes, and fibroblasts	glucocorticoids receptor (GR) is ubiquitous expressed in all skin cells	Major impact on the immune and inflammation system; Cell proliferation and survival via the PI3K/Akt pathway; Hair follicle proliferation and differentiation; Epidermal barrier formation.
Neurotrophins	Central nervous system; Skin sympathetic neurons, mast cells, T-cells and B-cells, keratinocytes, fibroblasts, and melanocytes	Two receptors TrK and p75 are expressed in mast cells, immune cells, keratinocytes, fibroblasts and melanocytes	Promote skin innervations; Promote survival and differentiation of mast cells, and modify inflammatory cytokines expressions; Promote proliferation of keratinocytes; Important for melanocytes migration, viability and differentiation and protect them from oxidative stress and apoptosis; Promote fibroblast differentiation and migration, and possibly contraction and MMP secretion.
Substance P	Sensory nerve fibers	Mast cells, macrophages, T-cells	Cytokine release to induce inflammation, activate mast cells, and induce lymphocyte proliferation Induce vascular permeability.
Prolactin	Pituitary gland; Skin hair follicle and epidermal keratinocytes, fibroblasts, adipocytes, sweat glands, and sebaceous glands	Prolactin receptor (PRLR) is ubiquitous expressed except in fibroblasts	Autocrine hair growth modulator by promoting catagen (hair regression); Stimulate keratinocytes growth and keratin production in keratinocytes; Sebum production in sebaceous glands; Immuno-modulation.
Catecholamines (epinephrine and norepinephrine)	Adrenal medulla; Skin nerve fibers, keratinocytes	adrenergic receptors are expressed by natural killer cells, monocytes, and T cells, keratinocytes and melanocytes	Regulate keratinocytes proliferation, differentiation, and migration; Promote melanogenesis in melanocytes; Decrease fibroblasts migration and collagen secretion and impair wound healing; Suppress IL-12 in dendritic cells leading to blunted Th1 and increased Th2 differentiation; Important for lymphocyte trafficking, circulation, proliferation, and cytokine production.