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CRH stimulates POMC activity and corticosterone production in dermal fibroblasts
Abstract
It has been previously documented that human skin cells including epidermal keratinocytes and dermal fibroblasts produce and process proopiomelanocortin (POMC), corticotropin releasing hormone (CRH), and express functional CRH receptors type-1 (CRH-R1). The skin also has corticosteroidogenic activity, suggesting a functional connection between these elements. In the current study, we found that human dermal fibroblasts (but not normal epidermal keratinocytes) respond to CRH with stimulation of cAMP, with POMC gene and protein expression, and ACTH production and release. Furthermore, CRH and ACTH stimulate production of corticosterone in fibroblasts, with ACTH being more potent. Although cortisol-immunoreactivity accumulation/production in fibroblasts has been detected by ELISA, it appears to be constitutive (not affected by CRH or ACTH). These effects are absent in keratinocytes. Therefore, we propose that fibroblasts but not keratinocytes display a functional CRH-POMC-corticosteroid axis organized similarly to the hypothalamus-pituitary-adrenal (HPA) axis. However, it diverges from the HPA organization in its distal step, where CRH and ACTH stimulate production of corticosterone, instead of cortisol.
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“We have also detected cortisol as well as corticosterone production in epidermal melanocytes and dermal fibroblasts (chemical structure was confirmed by LC/MS) [57, 58, 60].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [57]
In the citing paper
“In the skin, induction of steroidogenesis by CRH or ACTH, or factors raising intracellular cAMP levels appears to be cell type dependent because induced corticosterone and cortisol formation has been observed in normal and malignant epidermal melanocytes [53, 58] and dermal fibroblasts [57, 60], but not epidermal keratinocytes.”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [57]
In the citing paper
“The production of steroids in the skin after stimulation by CRH is strongly dependent on the CRH-R1 receptor [57–59].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [57]
Citations
Cites
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Chrousos, G. P. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505183322008 · Cited by 2,579
Slominski, A., Wortsman, J., Luger, T., Paus, R., & Solomon, S. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.979 · Cited by 776
Neuroendocrinology of the Skin1
Slominski, A., & Wortsman, J. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.5.0410 · Cited by 727
Neuroendocrinology of the Skin
Slominski, A. T. (2000) · Endocrine Reviews · doi:10.1210/er.21.5.457 · Cited by 508
Cutaneous expression of corticotropin-releasing hormone (CRH), urocortin, and CRH receptors
SLOMINSKI, A., WORTSMAN, J., PISARCHIK, A., ZBYTEK, B., LINTON, E. A., MAZURKIEWICZ, J. E., & WEI, E. T. (2001) · The FASEB Journal · doi:10.1096/fj.00-0850rev · Cited by 305 · cited 2×
“Evidence is accumulating that mediators known to be involved in the endocrine responses to systemic stress are also expressed or produced in the skin (Slominski and Wortsman, 2000; Slominski et al., 2000b, 2001; Slominski et al., 2003).”
BackgroundMast cells as targets of corticotropin-releasing factor and related peptides
Theoharides, T. C., Donelan, J., Papadopoulou, N., Cao, J., Kempuraj, D., & Conti, P. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.09.007 · Cited by 301
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Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes
Zouboulis, C. C., Seltmann, H., Hiroi, N., Chen, W., Young, M., Oeff, M., Scherbaum, W. A., Orfanos, C. E., McCann, S. M., & Bornstein, S. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.102180999 · Cited by 290
Cutaneous androgen metabolism: basic research and clinical perspectives
Chen, W., Thiboutot, D., & Zouboulis, C. C. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.00613.x · Cited by 273
Slominski, A., Zjawiony, J., Wortsman, J., Semak, I., Stewart, J., Pisarchik, A., Sweatman, T., Marcos, J., Dunbar, C., & C. Tuckey, R. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04356.x · Cited by 243
Self-citation
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Slominski, A. T., Zmijewski, M. A., Skobowiat, C., Zbytek, B., Slominski, R. M., & Steketee, J. D. (2012) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-642-19683-6 · Cited by 505
Melasma: a clinical and epidemiological review
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Slominski (2012) · doi:10.1007/978-3-642-19683-6_1 · Cited by 461
How UV Light Touches the Brain and Endocrine System Through Skin, and Why
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Key role of CRF in the skin stress response system
Slominski, A. T., Zmijewski, M. A., Zbytek, B., Tobin, D. J., Theoharides, T. C., & Rivier, J. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1092 · Cited by 400
Self-citationSteroidogenesis in the skin: Implications for local immune functions
Slominski, A., Zbytek, B., Nikolakis, G., Manna, P. R., Skobowiat, C., Zmijewski, M., Li, W., Janjetovic, Z., Postlethwaite, A., Zouboulis, C. C., et al. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.02.006 · Cited by 369
Taves, M. D., Gomez-Sanchez, C. E., & Soma, K. K. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00100.2011 · Cited by 293
Differential expression of HPA axis homolog in the skin
Slominski, A., Wortsman, J., Tuckey, R. C., & Paus, R. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.12.012 · Cited by 279
“…suggest that neural crest-derived melanocytes and hair follicles display activation sequences and feedback regulation that most closely reproduce key characteristics of the central HPA axis at the peripheral tissue/single cell levels (Ito et al., 2005; Slominski, 2006; Slominski et al., 2005f).”
BackgroundInfluentialSelf-citationCutaneous hypothalamic–pituitary–adrenal axis homolog: regulation by ultraviolet radiation
Skobowiat, C., Dowdy, J. C., Sayre, R. M., Tuckey, R. C., & Slominski, A. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00217.2011 · Cited by 269
Self-citationBrain-Skin Connection: Stress, Inflammation and Skin Aging
Chen, Y., & Lyga, J. W. (2014) · Inflammation & Allergy - Drug Targets · doi:10.2174/1871528113666140522104422 · Cited by 280
POMC: The Physiological Power of Hormone Processing
Harno, E., Ramamoorthy, T. G., Coll, A. P., & White, A. E. (2018) · Physiological Reviews · doi:10.1152/physrev.00024.2017 · Cited by 286
Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation
Serre, C., Busuttil, V., & Botto, J.-M. (2018) · International Journal of Cosmetic Science · doi:10.1111/ics.12466 · Cited by 255
Current concepts of metastasis in melanoma
Zbytek, B., Carlson, J. A., Granese, J., Ross, J. S., Mihm, M. C., & Slominski, A. T. (2008) · Expert Review of Dermatology · doi:10.1586/17469872.3.5.569 · Cited by 249
“CRHR1 responds to CRH with stimulation of production and release of pro-opiomelanocortinderived peptides by the pituitary and by the peripheral organs, including skin [151,152].”
BackgroundAberg, K. M., Radek, K. A., Choi, E., Kim, D.-K., Demerjian, M., Hupe, M., Kerbleski, J. F., Gallo, R. L., Ganz, T., Mauro, T. M., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31726 · Cited by 234
Stress-induced Interaction of Skin Immune Cells, Hormones, and Neurotransmitters
Pondeljak, N., & Lugović‐Mihić, L. (2020) · Clinical Therapeutics · doi:10.1016/j.clinthera.2020.03.008 · Cited by 268
Measuring cortisol in hair and saliva from dogs: coat color and pigment differences
Bennett, A., & Hayssen, V. (2010) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2010.04.003 · Cited by 222
Neuroendocrine signaling in the skin with a special focus on the epidermal neuropeptides
Slominski, A. T., Slominski, R. M., Raman, C., Chen, J. Y., Athar, M., & Elmets, C. A. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00147.2022 · Cited by 200
On the role of skin in the regulation of local and systemic steroidogenic activities
Slominski, A. T., Manna, P. R., & Tuckey, R. C. (2015) · Steroids · doi:10.1016/j.steroids.2015.04.006 · Cited by 188
“Thus, local steroidogenesis can be stimulated by skin derived CRH, ACTH and other factors that enhance intracellular cAMP [74, 99, 115-117, 132, 153, 155] and by cytokines [99, 155].”
Rousseau, K., Kauser, S., Pritchard, L. E., Warhurst, A., Oliver, R. L., Slominski, A. T., Wei, E. T., Thody, A. J., Tobin, D. J., & White, A. E. (2007) · The FASEB Journal · doi:10.1096/fj.06-7398com · Cited by 178
“This may reflect the effect of CRH on POMC gene expression, as it is similar to stimulation of the POMC gene in epidermal melanocytes in vitro (16) and in fibroblasts (33).”
BackgroundResultMelanocortin Receptor Ligands: New Horizons for Skin Biology and Clinical Dermatology
Böhm, M., Luger, T. A., Tobin, D. J., & García-Borrón, J. C. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700421 · Cited by 165
“There is strong evidence that MCs are important regulators of mammalian skin pigmentation (Abdel-Malek et al., 1999; Slominski et al., 2005b).”
BackgroundCorticosterone mediates the condition-dependent component of melanin-based coloration
Roulin, A., Almasi, B., Rossi-Pedruzzi, A., Ducrest, A., Wakamatsu, K., Mikšı́k, I., Blount, J. D., Jenni‐Eiermann, S., & Jenni, L. (2007) · Animal Behaviour · doi:10.1016/j.anbehav.2007.09.007 · Cited by 170
“This may have occurred in the pituitary gland, but also in feather buds, because mammalian hair follicle and dermal fibroblast of the skin display a functional HPA axis equivalent to the hypothalamice pituitaryeadrenal axis (Ito et al. 2005; Slominski et al. 2005).”
Corticotropin releasing hormone and the skin
Slominski, A. (2006) · Frontiers in bioscience · doi:10.2741/1966 · Cited by 157
“Specificity of the CRH effects was documented by the use of CRH-R1 antagonists antalarmin and alpha-helical-CRH-[9-41](59).”
Self-citationExtra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders
Slominski, R. M., Tuckey, R. C., Manna, P. R., Jetten, A. M., Postlethwaite, A., Raman, C., & Slominski, A. T. (2020) · Genes & Immunity · doi:10.1038/s41435-020-0096-6 · Cited by 155
Molecular Mechanisms of Neurogenic Inflammation of the Skin
Marek‐Józefowicz, L., Nedoszytko, B., Grochocka, M., Zmijewski, M. A., Czajkowski, R., Cubała, W. J., & Slominski, A. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24055001 · Cited by 164
Risk factors for facial melasma in women: a case–control study
Handel, A. C., Lima, P. B., Tonolli, V. M., Miot, L. D. B., & Miot, H. A. (2014) · British Journal of Dermatology · doi:10.1111/bjd.13059 · Cited by 153
Involvement of the corticotropin-releasing hormone system in the pathogenesis of acne vulgaris
Gancevičienė, R., Gražienë, V., Fimmel, S., & Zouboulis, C. C. (2008) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2008.08959.x · Cited by 146
Neuroendocrine System of the Skin
Slominski, A. T. (2005) · Dermatology · doi:10.1159/000087012 · Cited by 141
CRH functions as a growth factor/cytokine in the skin
Slominski, A. T., Zbytek, B., Pisarchik, A. V., Slominski, R. M., Zmijewski, M. A., & Wortsman, J. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20530 · Cited by 129
UVB activates hypothalamic-pituitary-adrenal axis in C57BL/6 mice
Skobowiat, C., & Slominski, A. T. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.450 · Cited by 126
Neuro–immuno–endocrinology of the skin: how environment regulates body homeostasis
Slominski, R. M., Raman, C., Jetten, A. M., & Slominski, A. T. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01107-x · Cited by 147
“…UVB, physical trauma (including wounding), changes in humidity, microbial factors and cutaneous pathological conditions (such as dermatoses, cancer and melanoma) through mechanisms that involve actions of CRH, ACTH, cytokines and factors that raise intracellular cAMP levels 3,77,102,103,137–139 .”
Skin as an endocrine organ: implications for its function
Slominski, A., Wortsman, J., Paus, R., Elias, P. M., Tobin, D. J., & Feingold, K. R. (2008) · Drug Discovery Today Disease Mechanisms · doi:10.1016/j.ddmec.2008.04.004 · Cited by 116
“Dermal fibroblasts respond to CRF and ACTH with enhanced production of corticosterone only [44]; though cortisol is produced constitutively in these cells [53].”
BackgroundSkobowiat, C., Sayre, R. M., Dowdy, J. C., & Slominski, A. T. (2013) · British Journal of Dermatology · doi:10.1111/bjd.12096 · Cited by 115
Hair cortisol: a parameter of chronic stress? Insights from a radiometabolism study in guinea pigs
Keckeis, K., Lepschy, M., Schöpper, H., Moser, L. B., Troxler, J., & Palme, R. (2012) · Journal of Comparative Physiology B · doi:10.1007/s00360-012-0674-7 · Cited by 119
“GC synthesis in cell populations of mammalian skin is evident from several studies (Slominski et al. 1999, 2000a, 2005a, 2006).”
Steroid synthesis by primary human keratinocytes; implications for skin disease
Hannen, R. F., Michael, A. E., Jaulim, A., Bhogal, R., Burrin, J. M., & Philpott, M. P. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.11.059 · Cited by 96
“The hair follicle has been reported to express elements of the hypothalamic–pituitary– adrenal (HPA) axis and to synthesise cortisol [16], sebocytes demonstrate the transformation of 22R-hydroxycholesterol to 17-hydroxypregnenolone [7], whilst melanocytes and fibroblasts have also been shown to produce corticosterone…”
BackgroundThe significance of CYP11A1 expression in skin physiology and pathology
Slominski, R. M., Raman, C., Elmets, C. A., Jetten, A. M., Slominski, A. T., & Tuckey, R. C. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111238 · Cited by 100
The role of corticotropin‐releasing hormone in immune‐mediated cutaneous inflammatory disease
Kane, M. O., Murphy, E. P., & Kirby, B. (2006) · Experimental Dermatology · doi:10.1111/j.1600-0625.2006.00382.x · Cited by 93
“They confirmed that messenger RNA (mRNA) for the ACTH receptor (MC-2) and three obligatory enzymes of steroid synthesis are expressed in normal and pathological human skin (32) and that the response of melanocytes (33) and dermal fibroblasts (34) to local CRH stimulation is organised similarly to the HPA axis.”
BackgroundStress-linked cortisol concentrations in hair: what we know and what we need to know
Sharpley, C. F., McFarlane, J. R., & Slominski, A. (2012) · revneuro · doi:10.1515/rns.2011.058 · Cited by 92
Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways
Slominski, A. T., Zmijewski, M. A., Semak, I. V., Zbytek, B., Pisarchik, A. V., Li, W., Zjawiony, J. K., & Tuckey, R. C. (2014) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/18715206113139990308 · Cited by 91
Slominski, A. T., Zmijewski, M. A., Semak, I., Sweatman, T., Janjetovic, Z., Li, W., Zjawiony, J. K., & Tuckey, R. C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004309 · Cited by 90
Self-citationSainte–Marie, Y., Toulon, A., Paus, R., Maubec, E., Cherfa, A., Grossin, M., Descamps, V., Clemessy, M., Gasc, J., Peuchmaur, M. M., et al. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060991 · Cited by 87
Without nerves, immunology remains incomplete –in vivo veritas
Shepherd, A. J., Downing, J. R., & Miyan, J. A. (2005) · Immunology · doi:10.1111/j.1365-2567.2005.02223.x · Cited by 83
Jozic, I., Vukelic, S., Stojadinović, O., Liang, L., Ramirez, H. A., Pastar, I., & Tomic‐Canic, M. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.11.036 · Cited by 83
“We found that GCs are synthesized in epidermis and regulate inflammatory response during acute injury (Slominski et al., 2007; Slominski et al., 2005a; Slominski et al., 2005b; Slominski et al., 2004; Stojadinovic et al., 2007; Vukelic et al., 2011), whereas stress was found to impair wound healing…”
BackgroundRole of neuropeptides, neurotrophins, and neurohormones in skin wound healing
Chéret, J., Lebonvallet, N., Carré, J., Misery, L., & Gall‐Ianotto, C. L. (2013) · Wound Repair and Regeneration · doi:10.1111/wrr.12101 · Cited by 90
Extra-adrenal glucocorticoid synthesis: immune regulation and aspects on local organ homeostasis
Talabér, G., Jondal, M., & Okret, S. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.05.007 · Cited by 80
Hennebert, O., Chalbot, S., Alran, S., & Morfin, R. (2007) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2007.03.026 · Cited by 79
Cutaneous glucocorticosteroidogenesis: securing local homeostasis and the skin integrity
Slominski, A. T., Manna, P. R., & Tuckey, R. C. (2014) · Experimental Dermatology · doi:10.1111/exd.12376 · Cited by 79
Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy
Brożyna, A. A., Slominski, R. M., Nedoszytko, B., Zmijewski, M. A., & Slominski, A. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158575 · Cited by 89
Skin steroidogenesis in health and disease
Nikolakis, G., Stratakis, C. A., Kanaki, T., Slominski, A., & Zouboulis, C. C. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9390-z · Cited by 76
Slominski, A. (2009) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2008.08958.x · Cited by 74
The role of neuropeptides in the multifactorial pathogenesis of acne vulgaris
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Neuroendocrinology of the skin
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“Sebocytes’ makeup” - Novel mechanisms and concepts in the physiology of the human sebaceous glands
Tóth, B. I., Oláh, A., Szöllősi, A. G., Czifra, G., & Bíró, T. (2011) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-0941-6 · Cited by 76
Samotij, D., Nedoszytko, B., Bartosińska, J., Batycka-Baran, A., Czajkowski, R., Dobrucki, I. T., Dobrucki, L. W., Górecka-Sokołowska, M., Janaszak‐Jasiecka, A., Krasowska, D., et al. (2020) · Advances in Dermatology and Allergology · doi:10.5114/ada.2020.94832 · Cited by 69
“This termination of CRH/urocortin- or cytokineinduced proinflammatory activities can be mediated via indirect effects involving stimulation of POMC, the production and release of corticosteroids [160, 161, 164, 166], and POMC-peptides dependent downregulation of NF-kb activities in a context-dependent fashion [187, 21…”
BackgroundCultured human dermal fibroblasts do produce cortisol
Slominski, A., Zbytek, B., Szczesniewski, A., & Wortsman, J. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700204 · Cited by 66
“In contrast, in human dermal fibroblasts cortisol production was not enhanced by corticotropin-releasing hormone and ACTH (there was only selective stimulation of corticosterone production; Slominski et al., 2005a).”
BackgroundMethodInfluentialSelf-citationKauser, S., Slominski, A. T., Wei, E. T., & Tobin, D. J. (2006) · The FASEB Journal · doi:10.1096/fj.05-5257com · Cited by 62
“hanced production of cortisol/corticosterone (13, 14).”
Zbytek, B., Wortsman, J., & Slominski, A. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0116 · Cited by 60
“28), at least, in melanocytes (22) and in fibroblasts (29).”
BackgroundMaubec, E., Laouenan, C., Deschamps, L., Nguyen, V. T., Scheer-Senyarich, I., Wackenheim-Jacobs, A.-C., Steff, M., Duhamel, S., Tubiana, S., Brahimi, N., et al. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.44 · Cited by 61
Kim, J. E., Cho, D. H., Kim, H. S., Kim, H. J., Lee, Y., Cho, B. K., & Park, H. J. (2006) · Experimental Dermatology · doi:10.1111/j.1600-0625.2006.00509.x · Cited by 59
Neuroendocrinology of the skin
Theoharides, T. C., Stewart, J. M., Taracanova, A., Conti, P., & Zouboulis, C. C. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9369-9 · Cited by 60
“CRH can stimulate corticosteroid production via ACTH from melanocytes [18], and it also stimulates POMC activity and corticosteroid production from dermal fibroblasts [19].”
BackgroundShaheen, B., & Gonzalez, M. (2012) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.2012.04516.x · Cited by 54
Putative role of HIF transcriptional activity in melanocytes and melanoma biology
Zbytek, B., Peacock, D. L., Seagroves, T. N., & Slominski, A. T. (2013) · Dermato-Endocrinology · doi:10.4161/derm.22678 · Cited by 53
Endocrine Controls of Skin Aging
Böhm, M., Stegemann, A., Paus, R., Kleszczyński, K., Maity, P., Wlaschek, M., & Scharffetter‐Kochanek, K. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnae034 · Cited by 59
The mineralocorticoid receptor as a novel player in skin biology: beyond the renal horizon?
Farman, N., Maubec, E., Pöeggeler, B., Klatte, J. E., Jaisser, F., & Paus, R. (2009) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.01011.x · Cited by 53
Increased glucocorticoid activation during mouse skin wound healing
Tiganescu, A., Hupe, M., Uchida, Y., Mauro, T. M., Elias, P. M., & Holleran, W. M. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0420 · Cited by 50
Dysfunctional Skin-Derived Glucocorticoid Synthesis Is a Pathogenic Mechanism of Psoriasis
Hannen, R. F., Udeh‐Momoh, C. T., Upton, J. H., Wright, M., Michael, A. E., Gulati, A., Rajpopat, S., Clayton, N., Halsall, D. J., Burrin, J. M., et al. (2017) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2017.02.984 · Cited by 51
Kim, H. S., Cho, D. H., Kim, H. J., Lee, J. Y., Cho, B. K., & Park, H. J. (2006) · Experimental Dermatology · doi:10.1111/j.1600-0625.2006.00443.x · Cited by 49
“: +82-2-3779-1230 Fax: +82-2-783-7604 e-mail: hjpark@catholic.ac.kr Accepted for publication 5 April 2006 Abbreviations: AA, alopecia areata; ACTH, adrenocorticotropic hormone; AEC, 3-amino-9-ethylcarbazole; CRH, corticotropinreleasing hormone; CRHR, CRH receptors; HPA, hypothalamic– pituitary–adrenal; a-MSH, a-melano…”
BackgroundInfluentialStress, the neuroendocrine system and mast cells: current understanding of their role in psoriasis
Harvima, I. T., & Nilsson, G. P. (2012) · Expert Review of Clinical Immunology · doi:10.1586/eci.12.1 · Cited by 47
Pharmacological and Genetic Inhibition of Caveolin-1 Promotes Epithelialization and Wound Closure
Jozic, I., Sawaya, A. P., Pastar, I., Head, C. R., Wong, L. L., Glinos, G. D., Wikramanayake, T. C., Brem, H., Kirsner, R. S., & Tomic‐Canic, M. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.07.016 · Cited by 46
“Cortisol levels in media (harvested from cultured skin) were measured using an ELISA kit (R&D Systems) following commercial protocol.(71) Cortisol concentration in media samples was normalized to the gram of tissue.”
MethodGenetic variation of the cutaneous HPA axis: an analysis of UVB-induced differential responses
Skobowiat, C., Nejati, R., Lu, L., Williams, R. W., & Slominski, A. T. (2013) · Gene · doi:10.1016/j.gene.2013.08.035 · Cited by 42
“…steroidogenic activity, which is similar to human skin (Slominski et al., 1996c; Slominski et al., 1999b; Slominski et al., 2004c; Ito et al., 2005; Slominski et al., 2005b; Slominski et al., 2005c; Cirillo and Prime, 2011; Hannen et al., 2011; Skobowiat et al., 2011; Vukelic et al., 2011;…”
BackgroundInfluentialHair melanocytes as neuro-endocrine sensors—Pigments for our imagination
Tobin, D. J., & Kauser, S. (2005) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2005.09.001 · Cited by 42
Adrenocorticotropin Hormone Stimulates Interleukin-18 Expression in Human HaCaT Keratinocytes
Park, H. J., Kim, H. J., Lee, J. Y., Cho, B. K., Gallo, R. L., & Cho, D. H. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700703 · Cited by 40
“Recent evidence suggests that CRH stimulation of corticosteroids production in melanocytes and dermal fibroblasts is mediated by ACTH (Slominski et al., 2005a, b).”
Kim, H. S., Cho, D. H., Kim, H. J., Lee, Y., Cho, B. K., & Park, H. J. (2006) · Experimental Dermatology · doi:10.1111/j.1600-0625.2006.00003.x · Cited by 40
CRH inhibits NF-κB signaling in human melanocytes
Zbytek, B., Pfeffer, L. M., & Slominski, A. T. (2006) · Peptides · doi:10.1016/j.peptides.2006.07.017 · Cited by 45
“In other cell types, such as keratinocytes, CRH did not stimulate POMC [32].”
BackgroundO’Kane, M., Markham, T., McEvoy, A. N., Fearon, U., Veale, D. J., FitzGerald, O., Kirby, B., & Murphy, E. P. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701023 · Cited by 38
“NURR1 expression in skin suggests similar pathways may operate locally since the skin is both a target and source of steroid hormones (Slominski et al., 2005) and recent reports confirm a local cutaneous hypothalamic–pituitary–adrenal-like system which responds to local stressors and may form part…”
BackgroundDonelan, J., Marchand, J. E., Kempuraj, D., Papadopoulou, N., Papaliodis, D., & Theoharides, T. C. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700153 · Cited by 37
Aoki, R., AOKI-YOSHIDA, A., Suzuki, C., & Takayama, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096804 · Cited by 36
“[5,30,31,32,33] Proinflammatory cytokines are potent inducers of endogenous cortisol.”
BackgroundGoswami, S., & Haldar, C. (2015) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2015.10.006 · Cited by 37
11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes
Itoi, S., Terao, M., Murota, H., & Katayama, I. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.09.065 · Cited by 35
Wierzbicka, J., Zmijewski, M. A., Piotrowska, A., Nedoszytko, B., Lange, M., Tuckey, R. C., & Slominski, A. T. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.08.006 · Cited by 35
“…known as cytochrome P450scc), was shown to metabolize 7-dehydroholesterol and vitamin D3 providing an alternative pathway of vitamin D activation (Slominski et al., 2005c; 2015b), with products including the low calcemic but biologically active secosteroids, 21(OH)pD which has a short (2C) side…”
BackgroundMethodInfluentialde Assis, L. V. M., Moraes, M. N., & Castrucci, A. M. D. L. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03183-5 · Cited by 33
Fischer, T. W., Bergmann, A., Kruse, N., Kleszczyński, K., Skobowiat, C., Slominski, A. T., & Paus, R. (2020) · British Journal of Dermatology · doi:10.1111/bjd.19115 · Cited by 33
Glucocorticoid metabolism in the developing lung: adrenal-like synthesis pathway
Provost, P. R., Boucher, E., & Tremblay, Y. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.03.004 · Cited by 31
“A similar situation was observed in human hair follicles and fibroblasts [119, 120] with negative feedback of GC on CRH expression [119].”
BackgroundTerao, M., Itoi, S., Murota, H., & Katayama, I. (2012) · Experimental Dermatology · doi:10.1111/exd.12075 · Cited by 30
Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction
Maharaj, A. V., Williams, J. L., Bradshaw, T. Y., Güran, T., Braslavsky, D. G., Casas, J., Chan, L. F., Metherell, L., & Prasad, R. (2020) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2020.105730 · Cited by 30
O’Sullivan, J. D. B., Peters, E. M. J., Amer, Y., Atuluru, P., Chéret, J., Rosenberg, A. M., Picard, M. A., & Paus, R. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2022.101008 · Cited by 32
Spaceflight Stressors and Skin Health
Radstake, W. E., Baselet, B., Baatout, S., & Verslegers, M. (2022) · Biomedicines · doi:10.3390/biomedicines10020364 · Cited by 27
Differentiation of Keratinocytes Modulates Skin HPA Analog
Wierzbicka, J., Zmijewski, M. A., Antoniewicz, J., Sobjanek, M., & Slominski, A. T. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25400 · Cited by 27
Mesdom, P., Colle, R., Lebigot, É., Trabado, S., Deflesselle, É., Fève, B., Becquemont, L., Corruble, E., & Verstuyft, C. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666191021141057 · Cited by 29
“and cognate receptors Ѵ Ѵ - [106-116]”
BackgroundPossible involvement of corticotropin-releasing factor receptor signaling on vascular inflammation
Inada, Y., Ikeda, K., Tojo, K., Sakamoto, M., Takada, Y., & Tajima, N. (2008) · Peptides · doi:10.1016/j.peptides.2008.10.015 · Cited by 24
“POMC mRNA is expressed, but not CYP11b1 and CYP11b2 mRNAs, in HAECs (Fig.”
BackgroundInfluentialRioux, G., Pouliot-Bérubé, C., Simard, M., Benhassine, M., Soucy, J., Guérin, S. L., & Pouliot, R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102923 · Cited by 25
Gravitational effects on fibroblasts’ function in relation to wound healing
Radstake, W. E., Gautam, K., Miranda, S., Rompay, C. V., Vermeesen, R., Tabury, K., Verslegers, M., Dowson, A., Gorissen, J., van Loon, J. J. W. A., et al. (2023) · npj Microgravity · doi:10.1038/s41526-023-00286-z · Cited by 23
Boudon, S. M., Vuorinen, A., Geotti-Bianchini, P., Wandeler, E., Kratschmar, D. V., Heidl, M., Campiche, R., Jackson, E., & Odermatt, A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0171079 · Cited by 21
Duarte, M., Pedrosa, S. S., Khusial, P. R., & Madureira, A. R. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111956 · Cited by 23
“For instance, in epidermal keratinocytes, CRH reduces proliferation by arresting cells during the G0/1 cycle and causes differentiation via calcium influx and AP-1 transcription pathway (Zbytek et al., 2005; Zbytek and Slominski, 2005).”
Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology
Cope, H., Elsborg, J., Demharter, S., McDonald, J. T., Wernecke, C., Parthasarathy, H., Unadkat, H., Chatrathi, M., Claudio, J., Reinsch, S. S., et al. (2024) · Communications Medicine · doi:10.1038/s43856-024-00532-9 · Cited by 19
On the role of environmental humidity on cortisol production by epidermal keratinocytes
Zhu, G. G., Janjetović, Z., & Slominski, A. T. (2013) · Experimental Dermatology · doi:10.1111/exd.12275 · Cited by 17
A Novel Role of Peripheral Corticotropin-Releasing Hormone (CRH) on Dermal Fibroblasts
Rassouli, O., Liapakis, G., Lazaridis, I., Sakellaris, G., Gkountelias, K., Gravanis, A., Margioris, A. N., Karalis, K. P., & Venihaki, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021654 · Cited by 18
“CRH and its receptors (CRF1, CRF2) are expressed in many peripheral tissues and organs including skin [22] where it has dual activity, direct proinflammatory and indirect anti-inflammatory [23] [24] [25].”
BackgroundCho, K., Kim, H. J., Kim, Y., Park, M., & Woo, S. (2019) · International Archives of Allergy and Immunology · doi:10.1159/000494624 · Cited by 17
Cumer, T., Machado, A. P., San‐Jose, L. M., Ducrest, A., Simon, C., Roulin, A., & Goudet, J. (2024) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2023.1995 · Cited by 15
“The peptidic hormone α -MSH is produced through the cleavage of the pro-opiomelanocortin protein, encoded by the POMC gene, whose transcription can be activated by the binding of CRH (corticotropin-stimulating hormone) to its receptor CRHR1 [51].”
BackgroundPaus, R., Ramot, Y., Kirsner, R. S., & Tomic‐Canic, M. (2020) · Experimental Dermatology · doi:10.1111/exd.14156 · Cited by 15
Critical role of keratinocytes in cutaneous immune responses
Gupta, R. K., Wasnik, P., Mondal, D., & Shukla, D. (2024) · Exploration of Immunology · doi:10.37349/ei.2024.00155 · Cited by 19
Metadata
- Authors
- Slominski, A., Zbytek, B., Semak, I., Sweatman, T., & Wortsman, J.
- Affiliations
- University of Tennessee Health Science Center (US)
- Belarusian State University (BY)
- SIU Medicine (US)
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 162
- Issue
- 1-2
- Pages
- 97-102
- ISSN
- 0165-5728 (ISSN-L)
- OpenAlex
- W2073828630
- Cited by
- 143
- References
- 28
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 4 · 2016: 9 · 2015: 5 · 2014: 9 · 2013: 11 · 2012: 13
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Johnson and Johnson
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 047079, R01AR047079)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- corticotropin-releasing factor, proopiomelanocortin, dermal fibroblasts, epidermal keratinocytes, corticosterone production, ACTH, CRH receptor type 1, cAMP signaling, hypothalamic-pituitary-adrenal axis, cortisol
- MeSH terms
- CRF Receptor, Type 1, Cyclic AMP, Adrenocorticotropic Hormone, Cells, Cultured, Chromatography, High Pressure Liquid, Corticosterone, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Fibroblasts, Colforsin, Gene Expression Regulation, Humans, Pro-Opiomelanocortin, RNA, Messenger, Skin, Time Factors, Blotting, Northern, Blotting, Western, Receptors, Corticotropin-Releasing Hormone, Reverse Transcriptase Polymerase Chain Reaction
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