Sensing the Environment: Regulation of Local and Global Homeostasis by the Skin's Neuroendocrine System

Słomiński, Andrzej; Żmijewski, Michał A.; Skobowiat, Cezary; Zbytek, Blazej; Slominski, Radomir M.; Steketee, Jeffery D.

doi:10.1007/978-3-642-19683-6

Cited by 399 publications

(544 citation statements)

References 462 publications

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“…Recent findings have indicated that both mechanisms contribute to local GC levels and a large body of evidence supports the hypothesis that human skin is capable of generating appreciable levels of GC through steroidogenesis (reviewed in Slominski et al 2012). However, here we demonstrate that the contribution made by steroidogenesis in mouse skin is negligible compared with GC activation by 11b-HSD1, which generates corticosterone at concentrations capable of GR activation (Dong et al 2006).…”

Section: Discussionsupporting

confidence: 80%

“…Previous studies have also established a role for extraadrenal GC generation from cholesterol in skin (reviewed by Slominski et al 2012). Expression of steroidogenic enzymes in this pathway, including cytochromes CYP11A1, CYP17A1, and CYP21A2 has been detected in human skin (Slominski et al 1996), with cortisol synthesis detected in hair follicles (Ito et al 2005), keratinocytes (Cirillo & Prime 2011, Hannen et al 2011, Vukelic et al 2011, melanocytes (Slominski et al 2005a), and fibroblasts (Slominski et al 2005b(Slominski et al , 2006.…”

Section: Introductionmentioning

confidence: 99%

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Increased glucocorticoid activation during mouse skin wound healing

Tiganescu

Hupe

Uchida

et al. 2014

Journal of Endocrinology

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Glucocorticoid (GC) excess inhibits wound healing causing increased patient discomfort and infection risk. 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) activates GCs (converting 11-dehydrocorticosterone to corticosterone in rodents) in many tissues including skin, where de novo steroidogenesis from cholesterol has also been reported. To examine the regulation of 11b-HSD1 and steroidogenic enzyme expression during wound healing, 5 mm wounds were generated in female SKH1 mice and compared at days 0, 2, 4, 8, 14, and 21 relative to unwounded skin. 11b-HSD1 expression (mRNA and protein) and enzyme activity were elevated at 2 and 4 days post-wounding, with 11b-HSD1 localizing to infiltrating inflammatory cells. 11b-HSD2 (GC-deactivating) mRNA expression and activity were undetectable. Although several steroidogenic enzymes displayed variable expression during healing, expression of the final enzyme required for the conversion of 11-deoxycorticosterone to corticosterone, 11b-hydroxylase (CYP11B1), was lacking in unwounded skin and post-wounding. Consequently, 11-deoxycorticosterone was the principal progesterone metabolite in mouse skin before and after wounding. Our findings demonstrate that 11b-HSD1 activates considerably more corticosterone than is generated de novo from progesterone in mouse skin and drives GC exposure during healing, demonstrating the basis for 11b-HSD1 inhibitors to accelerate wound repair.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Increased glucocorticoid activation during mouse skin wound healing

Tiganescu

Hupe

Uchida

et al. 2014

Journal of Endocrinology

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“…The skin is the largest organ in the body, located at the interphase between the external and internal environment, requiring development of efficient sensory and effector capabilities to differentially react to changes in the environment [1]. The dermis is a 1.0-3.0-mm-thick layer of the skin on the inner side of the epidermis.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Ultraviolet Radiation Wavelengths Causing Hardening and Reduced Elasticity of Collagen Gels In Vitro

Maeda

2018

Cosmetics

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Regular exposure of facial skin to sunlight promotes wrinkle formation; ultraviolet (UV) radiation causes the skin to harden and lose its elasticity. To study UV damage to the skin in vitro, a short-term in vitro photoaging model is required. Hence, the UV transmittance of excised human skin was measured. Changes in elasticity in the cheeks of humans of different ages were investigated. Moreover, changes in the hardness and elasticity of collagen gels following UV exposure were investigated. UV rays penetrated the upper layer of the dermis and UVA (330 nm) rays penetrated approximately 1.6 times farther than UVB (310 nm) rays. A correlation between age and lower cheek elasticity was observed. Upon exposure to UV rays, collagen gels hardened and their elasticity decreased; UVA rays exhibited a stronger effect than UVB rays. Wavelengths of 300-340 nm caused hardening and reduced elasticity of collagen gels; 330-nm radiation showed the most pronounced effect. These effects were not observed upon exposure to UV wavelengths over 350 nm. Investigating the UV-hardening mechanism of collagen showed increased tyrosine crosslinks (dityrosines) in the in vitro model of photodamage to collagen, suggesting that dityrosine formation contributes to hardening and reduced elasticity of collagen in photoaged skin.

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“…1,27) The classical neuroendocrine axes such as the cutaneous HPA and hypothalamic-thyroid axis (HPT) exist in the skin, making the skin be an important peripheral neuro-endocrine-immune organ. 23,28) Given their common embryonic origins, it is not surprising that skin shares numerous mediators with the nervous and endocrine system. 1,11,29,30) 5-HT is a recognized neurotransmitter and molecular signal that distributes brain-wide with particular presence in hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

Zhou

Ling

Ping

2016

Biological & Pharmaceutical Bulletin

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Interferon-γ (IFN-γKey words interferon-γ (IFN-γ); 5-hydroxytryptamine (5-HT); cross-talk; melanogenesis; migration Skin is the largest organ in human body, which plays a role as biologically active barrier to the external environment. It acts not only as a target for neuroendocrine signals but also a source of hormones and neurotransmitters, particularly the epidermis.1) Epidermis and dermis are the two main parts of skin. Epidermal melanocytes, derived from the neural crest, can produce melanin to absorb ultraviolet radiation and provide photoprotection.2) Melanin is synthesized in melanosomes, which are specialized lysosomerelated organelle (LRO) of pigment cells devoting to the biosynthesis, storage and transport of melanin.3) Melanosomes undergo 4 maturation stages, each characterized by unique ultrastructural morphology and melanin content. 4,5) The principal role of the melanocyte is to produce the pigment within melanosomes and to transfer these organelles to upwards of 40 keratinocytes, which are neighboring melanocyte to constitute the 'epidermal melanin unit.' Melanocyte transport melanosomes from the formation site in the cell center to the principal site of transfer at dendritic tips. Accomplishing this feat, melanocyte needs to couple long-range, bidirectional microtubule-dependent transport of melanosomes along the length of dendrites with the capture and local movement of the organelles in actin-rich dendritic tips by the actin-based motor protein myosin Va. 5,6) Studies have shown that there are four possible mechanisms described for melanosome transfer, including the cytophagocytosis model, membrane fusion model, shedding-phagocytosis model and exocytosis-endocytosis model. 6) In addition, multifarious signaling pathways and transcription factors firmly manage melanocyte migration. These proteins and pathways provide and integrate signals to create the proper environment for its normal development and migration. 2)Melanin biosynthesis process is under a complex control mediated by multiple elements through different pathways. A series of pigment cell-specific melanosomal proteins are responsible for melanogenesis, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT). 7-9) Skin cells can produce hormones, neurotransmitters and neuropeptides and corresponding functional receptors, owing to which constitute the cutaneous equivalent of the hypothalamic-pituitary-adrenal (HPA) axis.10,11) It has recently uncovered that cutaneous expression of the biochemical machinery involved in the sequential transformation of L-tryptophan to serotonin and melatonin. 12,13) Serotonin 5-hydroxytryptamine (5-HT) is a neurotransmitter whose actions are mediated via an interaction with receptors, including seven families (5-HT 1-7 receptors) with at least 21 subtypes. Skin cells express mRNA encoding 5-HT receptors, 5-HT 1A, -1B, -2A, -2B, -2C, and -7 receptor.14,15) 5-HT 2A receptor was reported participating in the regulatory processes of 5-HT on melanogenesis.16) Our preli...

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Sensing the Environment: Regulation of Local and Global Homeostasis by the Skin's Neuroendocrine System

Cited by 399 publications

References 462 publications

Increased glucocorticoid activation during mouse skin wound healing

Increased glucocorticoid activation during mouse skin wound healing

Analysis of Ultraviolet Radiation Wavelengths Causing Hardening and Reduced Elasticity of Collagen Gels In Vitro

Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

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