The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
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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In the citing paper
“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
The Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated Inflammation
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
Thiboutot, D., Gilliland, K., Cong, Z., Jabara, S., McAllister, J. M., Sivarajah, A., & Clawson, G. (2003) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2003.12244.x · Cited by 301
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
Cited by
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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
Handel, A. C., Miot, L. D. B., & Miot, H. A. (2014) · Anais Brasileiros de Dermatologia · doi:10.1590/abd1806-4841.20143063 · Cited by 461
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
Slominski, A. T., Zmijewski, M. A., Plonka, P. M., Szaflarski, J. P., & Paus, R. (2018) · Endocrinology · doi:10.1210/en.2017-03230 · Cited by 452
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-citation
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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