The skin, the body's largest organ, is strategically located at the interface with the external environment where it detects, int...
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The skin, the body's largest organ, is strategically located at the interface with the external environment where it detects, integrates and responds to a diverse range of stressors, including solar radiation. It has already been established that the skin is an important peripheral neuroendocrine-immune organ that is closely networked with central regulatory systems. These capabilities contribute to the maintenance of peripheral homeostasis. Specifically, epidermal and dermal cells produce and respond to classical stress neurotransmitters, neuropeptides and hormones, production which is stimulated by ultraviolet radiation (UVR), biological factors (infectious and non-infectious) and other physical and chemical agents. Examples of local biologically active products are cytokines, biogenic amines (catecholamines, histamine, serotonin and N-acetyl-serotonin), melatonin, acetylocholine, neuropeptides including pituitary (proopiomelanocortin-derived ACTH, b-endorphin or MSH peptides, thyroid stimulating hormone) and hypothalamic (corticotropin-releasing factor and related urocortins, thyroid-releasing hormone) hormones, as well as enkephalins and dynorphins, thyroid hormones, steroids (glucocorticoids, mineralocorticoids, sex hormones, 7-d steroids), secosteroids, opioids and endocannabinoids. The production of these molecules is hierarchical, organized along the algorithms of classical neuroendocrine axes such as the hypothalamic pituitary adrenal axis (HPA), hypothalamic-thyroid axis (HPT), serotoninergic, melatoninergic, catecholaminergic, cholinergic, steroid/secosteroidogenic, opioid and endocannabinoid systems. Disruptions of these axes or of communication between them may lead to skin and/or systemic diseases. These local neuroendocrine networks also serve to limit the effect of noxious environmental agents to preserve local and consequently global homeostasis. Moreover, the skin-derived factors/systems can also activate cutaneous nerve endings to alert the brain to changes in the epidermal or dermal environments, or alternatively to activate other coordinating centers by direct (spinal cord) neurotransmission without brain involvement. Furthermore, rapid and reciprocal communications between epidermal and dermal and adnexal compartments are also mediated by neurotransmission including antidromic modes of conduction. Lastly, skin cells and the skin as an organ coordinate and/or regulate not only peripheral but also global homeostasis. Résumé 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. Contenu Introduction.- Biogenic amines in the skin.- Melatoninergic system in the skin.- Cutaneous cholinergic system.- Corticotropin signaling system in the skin.- Steroidogenesis in the skin.- Equivalent of hypothalamo-pituitary adrenal axis in the skin.- Cutaneous secosteroidal system.- Equivalent of hypthalamic-pituitary-thyroid axis.- Cutaneous opioid system.- Cutaneous endocannabinoid system.- Perspectives.- References.- Subject index.
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Sensing the Environment: Regulation of Local and Global Homeostasis by the Skin's Neuroendocrine System