How UV Light Touches the Brain and Endocrine System Through Skin, and Why

Abstract

The skin, a self-regulating protective barrier organ, is empowered with sensory and computing capabilities to counteract the environmental stressors to maintain and restore disrupted cutaneous homeostasis. These complex functions are coordinated by a cutaneous neuro-endocrine system that also communicates in a bidirectional fashion with the central nervous, endocrine, and immune systems, all acting in concert to control body homeostasis. Although UV energy has played an important role in the origin and evolution of life, UV absorption by the skin not only triggers mechanisms that defend skin integrity and regulate global homeostasis but also induces skin pathology (e.g., cancer, aging, autoimmune responses). These effects are secondary to the transduction of UV electromagnetic energy into chemical, hormonal, and neural signals, defined by the nature of the chromophores and tissue compartments receiving specific UV wavelength. UV radiation can upregulate local neuroendocrine axes, with UVB being markedly more efficient than UVA. The locally induced cytokines, corticotropin-releasing hormone, urocortins, proopiomelanocortin-peptides, enkephalins, or others can be released into circulation to exert systemic effects, including activation of the central hypothalamic-pituitary-adrenal axis, opioidogenic effects, and immunosuppression, independent of vitamin D synthesis. Similar effects are seen after exposure of the eyes and skin to UV, through which UVB activates hypothalamic paraventricular and arcuate nuclei and exerts very rapid stimulatory effects on the brain. Thus, UV touches the brain and central neuroendocrine system to reset body homeostasis. This invites multiple therapeutic applications of UV radiation, for example, in the management of autoimmune and mood disorders, addiction, and obesity.

Figure 1.

UV radiation as an initiator and driver of biological evolution. According to the second thermodynamic law, any self-organization must be driven by an irreversible process of energy flow in the form of low-entropy radiation from a container of high temperature (the Sun), and dissipate it in the form of high-entropy radiation in a container of low temperature (the space). UV radiation is enough to drive chemical reactions independently on metabolism and to damage the cell. DNA effectively dissipates the energy of excitation (19) and can store genetic information including only a limited number of UV-induced mutations. The cell also gets information on UV to set off the processes of repair and photoprotection, thus maintaining homeostasis, preserving enthalpy, and facilitating evolution. (The background: Hubble Deep Field; NASA, https://www.nasa.gov/. The DNA icon: PngTree, https://pngtree.com/free-icons.)

Figure 2.

Skin neuroendocrine system. The skin neuroendocrine system integrates locally and centrally produced classical neuroendocrine or endocrine signaling molecules, thus providing a natural platform of interaction between internal organs and environment. To respond to a variety of internal and external signals, skin cells not only are sensitive to neurohormonal regulation but also produce elements of the HPA axis or hypothalamic-pituitary-thyroid axis, as well as other neuropeptides, biogenic amines, serotonin, melatonin, NO, opioids, cannabinoids, catecholamines, acetylcholine, steroids, secosteroids, and growth factors adipokines and cytokines. Skin’s neuroendocrine system comprises epidermal and dermal cells including resident immune cells, nerve endings, and sensory receptors in the skin and its appendages. BM, basement membrane; IC, immune cells; HPT, hypothalamic-pituitary-thyroid.

Figure 3.

The interaction between the skin’s endocrine system and central neuroendocrine system in stress response. The skin stress response system can activate central neuroendocrine responses with its direct homeostatic, metabolic, and phenotypic consequences. The crosstalk between local and central elements of stress response is maintained by bidirectional neuronal stimulation through naked nerve endings in the epidermis and innervation of adnexal structures (hair follicles; sebaceous, eccrine, and apocrine glands; arrector pili muscle). Active neuroendocrine mediators could also be directly secreted in response to stimuli by neurons, epidermal keratinocytes, melanocytes, and Langerhans cells, as well as dermal residing mast cells, macrophages, and fibroblasts or infiltrating lymphocytes and granulocytes. Furthermore, the circulatory system provides an additional route for an exchange of signaling molecules between the skin’s neuroendocrine system and central endocrine organs, including elements of the HPA axis. Constant exchange of neuroendocrine mediators between skin and other organs is responsible for the maintenance of local and global homeostasis and skin response to external and internal signals. BM, basement membrane; F, fibrocytes/fibroblasts; IC, immune cells; K, keratinocytes; LC, Langerhans cells; M, melanocytes.

Figure 4.

Melanocyte as the computing UV sensor, effector, and master regulator in the epidermal neuroendocrine concert. Melanocytes—melanin-producing cells with neuroendocrine capabilities (122, 218)—after receiving UV electromagnetic waves, decode them according to their frequency, translate the absorbed energy/information into biologically relevant signals and activities, and convey them to multiple effector targets (217, 218). The UV-induced formation of multiple dendrites (122, 128, 212, 220) allows them not only to amplify the biological effect (right, output) but also to enhance the capability of sensing UV-induced disturbances in epidermal homeostasis by collecting information from multiple structures at different, sometimes distant spaciotemporal locations (left, input). hv, a quantum of UV irradiation.