Proopiomelanocortin, corticotropin releasing hormone and corticotropin releasing hormone receptor genes are expressed in human skin

Slominski, Andrzej; Ermak, Gennady; Hwang, Jim; Chakraborty, Ashok; Mazurkiewicz, Joseph E.; Mihm, Martín C.

doi:10.1016/0014-5793(95)01090-2

Cited by 159 publications

(167 citation statements)

References 17 publications

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“…CRH and related peptides-Skin cells produce CRH and the related peptides urocortin (urc) 1 and 2 (Roloff et al, 1998;Slominski et al, 1995;Slominski et al, 1996c;Slominski et al, 1998b;Slominski et al, 2000c;Slominski et al, 1999c). In human skin, the production of CRH is associated with changes in the expression of the CRH gene, which is stimulated by UV radiation and forskolin and inhibited by dexamethasone (Slominski et al, 1996a;Slominski et al, 1998b;Zbytek et al, 2006).…”

Section: Cutaneous Crh Signaling Systemmentioning

confidence: 99%

“…CRH receptors-CRH-R1 and CRH-R2 are expressed in human Slominski et al, 1995;Slominski et al, 2000d;Slominski et al, 2001;Slominski et al, 1999c) and rodent (Pisarchik and Slominski, 2002;Roloff et al, 1998;Slominski et al, 1996c;Slominski et al, 2000d;Slominski et al, 1999c) skin, with species-specific compartmental localization. In the human skin, CRH-R1 is predominantly expressed in the epidermis with CRH-R1α being the major isoform present (Slominski et al, 2004a).…”

Section: Cutaneous Crh Signaling Systemmentioning

confidence: 99%

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Differential expression of HPA axis homolog in the skin

Slominski

Wortsman

Tuckey

et al. 2007

Molecular and Cellular Endocrinology

259

267

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SummaryHuman skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including proopiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes glucocorticoids. Expression of these elements is organized in functional, cell type-specific regulatory loops, which imitate the signaling structural hierarchy of the HPA axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates POMC expression and production of ACTH through activation of cAMP dependent pathway(s). Melanocytes respond with enhanced production of cortisol and corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH and ACTH with enhanced production of corticosterone, but not cortisol, which is produced constitutively. Organcultured human scalp hair follicles also show a fully functional HPA axis equivalent, including cortisol synthesis and secretion and negative feedback regulation by cortisol on CRH expression. Thus differential, CRH-driven responses of skin reproduce key features of the central HPA axis at the tissue/single cell levels.

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Section: Cutaneous Crh Signaling Systemmentioning

confidence: 99%

Section: Cutaneous Crh Signaling Systemmentioning

confidence: 99%

Differential expression of HPA axis homolog in the skin

Slominski

Wortsman

Tuckey

et al. 2007

Molecular and Cellular Endocrinology

259

267

View full text Add to dashboard Cite

show abstract

“…In addition, cholesterol, a precursor from which steroid hormones are synthesized, is produced by skin (31). All major components of HPA axis (CRH, CRH-R, urocortin, POMC, ACTH, MC-R) and critical enzymes necessary for GCs synthesis are produced and identified in skin (32)(33)(34)(35)(36). In addition, isolated hair follicles, dermal fibroblasts, and melanocytes secrete cortisol and display HPA axis-like regulatory feedback systems (37)(38)(39).…”

mentioning

confidence: 99%

Cortisol Synthesis in Epidermis Is Induced by IL-1 and Tissue Injury

Vukelic

Stojadinović

Pastar

et al. 2011

Journal of Biological Chemistry

176

196

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Glucocorticoids (GCs) are known inhibitors of wound healing. In this study we report the novel finding that both keratinocytes in vitro and epidermis in vivo synthesize cortisol and how this synthesis regulates wound healing. We show that epidermis expresses enzymes essential for cortisol synthesis, including steroid 11 ␤-hydroxylase (CYP11B1), and an enzyme that controls negative feedback mechanism, 11␤-hydroxysteroid dehydrogenase 2 (11␤HSD2). We also found that cortisol synthesis in keratinocytes and skin can be stimulated by ACTH and inhibited by metyrapone (CYP11B1 enzyme inhibitor). Interestingly, IL-1␤, the first epidermal signal of tissue injury, induces the expression of CYP11B1 and increases cortisol production by keratinocytes. Additionally, we found induction of CYP11B1 increased production of cortisol and activation of GR pathway during wound healing ex vivo and in vivo using human and porcine wound models, respectively. Conversely, inhibition of cortisol synthesis during wound healing increases IL-1␤ production, suggesting that cortisol synthesis in epidermis may serve as a local negative feedback to proinflammatory cytokines. Local GCs synthesis, therefore, may provide control of the initial proinflammatory response, preventing excessive inflammation upon tissue injury. Inhibition of GC synthesis accelerated wound closure in vivo, providing the evidence that modulation of cortisol synthesis in epidermis may be an important regulatory mechanism during wound healing.Acute wound healing is a complex biological process mediated by a network of signaling pathways that coordinate multiple cellular processes, including cellular migration and proliferation, ultimately leading to barrier restoration (1). Wound healing is a tightly spatiotemporally regulated process, and changes in any component of this process can be detrimental, leading to further tissue damage or impairment of healing (2, 3).For example, timing of inflammatory response is essential; proinflammatory signals are important in the early stage of healing, but they can be detrimental if they persist (4, 5), underscoring a need for tight control of both stimulators and inhibitors during the wound healing process.Upon injury, keratinocytes are the first cells that respond (6, 7) by releasing pre-stored interleukin-1 (IL-1) (8). IL-1 has an autocrine and a paracrine function; that is, to activate keratinocytes and to alert the surrounding cells and tissues. The release of IL-1 by keratinocytes, with subsequent release of additional signaling molecules (9, 10), demarcates the proinflammatory phase of wound healing. In response to these signals, activated keratinocytes start migrating and proliferating (7,8,11). Successful repair after tissue injury requires resolution of inflammatory response, transitioning keratinocyte (HEK) from activated to differentiating phenotype. However, very little is known about endogenous epidermal signals that control keratinocyte activation cycle and inflammatory response.Epidermal keratinocytes have important immunol...

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“…related peptides (Slominski et al, 2000c;Slominski et al, 2001), which led to the proposal that the CRF/URC signaling system may play a central role in the skin's response to stress (Slominski et al, 1999;Slominski et al, 2000d;; skin produces CRF and URC and expresses CRF-R1 Roloff et al, 1998;Slominski et al, 1995;Slominski et al, 1996;Slominski et al, 1998;Slominski et al, 2000a;Slominski et al, 2000c). These CRF-Rs are functional, e.g., they respond to CRF and URC through activation of receptor(s)-mediated pathways to modify skin cell phenotype (Fazal et al, 1998;Quevedo et al, 2001;Slominski et al, 1999;Slominski et al, 2000b;.…”

mentioning

confidence: 99%

Intracellular calcium measurements of single human skin cells after stimulation with corticotropin-releasing factor and urocortin using confocal laser scanning microscopy

Wiesner¹,

Roloff²,

Fechner³

et al. 2003

Journal of Cell Science

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Using confocal laser scanning microscopy we investigated the Ca2+ distribution in single corticotropin releasing factor- and urocortin-stimulated human skin cells. The models tested included melanoma cells, neonatal melanocytes and keratinocytes, and immortalized HaCaT keratinocytes. The changes in intracellular Ca2+ signal intensities observed after stimulation of different cell types with corticotropin releasing factor and urocortin showed that: (1) the increase of intracellular Ca2+ concentration was caused by a Ca2+ influx(inhibition by EGTA); (2) this Ca2+ influx took place through voltage-activated Ca2+ ion channels (inhibition by d-cis-diltiazem,verapamil) and (3) cyclic nucleotide-gated ion channels were not involved in this process (no effect of Mg2+). The effects were also observed at very low peptide concentrations (10-13 M) with no apparent linear correlation between peptide dosage and increase of fluorescence intensity,which implied co-expression of different corticotropin releasing factor receptor forms in the same cell. Immortalized (HaCaT) keratinocytes exhibited the strongest differential increases of a Ca2+ fluorescence after peptide-stimulation. Corticotropin releasing factor induced Ca2+flux into the cytoplasm, while urocortin Ca2+ flux into the nucleus with a remarkable oscillatory effect. The latter indicated the presence of an intracellular urocortin-induced signal transduction pathway that is unique to keratinocytes.

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Proopiomelanocortin, corticotropin releasing hormone and corticotropin releasing hormone receptor genes are expressed in human skin

Cited by 159 publications

References 17 publications

Differential expression of HPA axis homolog in the skin

Differential expression of HPA axis homolog in the skin

Cortisol Synthesis in Epidermis Is Induced by IL-1 and Tissue Injury

Intracellular calcium measurements of single human skin cells after stimulation with corticotropin-releasing factor and urocortin using confocal laser scanning microscopy

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