Described as the body's largest organ, the skin is strategically located
at the interface with the external environment where it has evolved to
detect, integrate and respond to a diverse range of stressors including
UV radiation. Recent findings have established the skin as a peripheral
neuroendocrine organ that is tightly networked to central stress axes.
This capability contributes to the maintenance of skin's and body's
homeostasis. Specifically, epidermal and dermal cells produce and
respond to classical stress neurotransmitters, neuropeptides and
hormones, and this production is modified by ultraviolet radiation and
biological, chemical and physical factors. Examples of potent epidermal
products include biogenic amines (catecholamines, serotonin and
N-acetyl-serotonin), acetylcholine, melatonin and its metabolites,
proopiomelanocortin-derived ACTH, b-endorphin and MSH peptides,
corticotropin-releasing factor and related urocortins, corticosteroids
and their precursor molecules, thyroid-related hormones, opioids and
cannabinoids. The production of these molecules in the skin is
hierarchical, following the algorithms of classical neuroendocrine axes
(e.g. hypothalamic pituitary adrenal axis (HPA), hypothalamic-thyroid
axis, serotoninergic/melatoninergic, catecholaminergic and cholinergic
systems). The deregulation of these systems may be involved in the
etiology of some skin diseases. These local neuroendocrine systems
represent exquisite regulatory levels addressed at restricting the
effect of noxious agents to preserve local and, consequently, global
body's homeostasis and adapt to changing external environment.
Furthermore, the skin-derived signals may also activate cutaneous
sensory nerve endings to alert the brain on environment- or
pathology-induced changes in the epidermal and dermal milieau, or
alternatively, to activate other coordinating centers by spinal cord
neurotransmission with, or without brain's involvement. Finally, the
local neuroendocrine system will imprint resident and circulating immune
cells to act as cellular messengers sent to other organs to coordinate
responses to the changing environment.
