Perspectives

Abstract

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 (Fig. 1.2). 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) (Figs. 2.1–2.3), acetylcholine, melatonin and its metabolites (Figs. 2.5 and 3.1), proopiomelanocortin-derived ACTH, β-endorphin and MSH peptides, corticotropin-releasing factor and related urocortins (Figs. 5.1, 5.2, 7.3 and 7.4), corticosteroids and their precursor molecules, thyroid-related hormones (Fig. 9.1), 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 (Fig. 1.1). 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 (1.1).