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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–144 of 144
UVB‐inhibited H19 activates melanogenesis by paracrine effects
Pei, S., Huang, J., Chen, J., Hu, S., Lei, L., Fu, C., Jiang, L., Ding, Y., Leng, Y., Huang, L., et al. (2018) · Experimental Dermatology · doi:10.1111/exd.13749 · Cited by 15
Son, B., Kang, W., Park, S., Choi, D., & Park, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179273 · Cited by 16
Cell type-specific regulatory effects of glucocorticoids on cutaneous TLR2 expression and signalling
Su, Q., Pfalzgraff, A., & Weindl, G. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2017.03.023 · Cited by 14
Skin Diseases in Elite Athletes
Liebich, C., Wergin, V. V., Marquart, C., Schubert, I., von Bruehl, M., Halle, M., Oberhoffer, R., & Wolfarth, B. (2021) · International Journal of Sports Medicine · doi:10.1055/a-1446-9828 · Cited by 12
Chen, W., Yan, Z., Liu, S., Zhang, G., Sun, D., & Hu, S. (2011) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-011-1606-7 · Cited by 11
“The Amount of POMC Derivative in Pituitary The amount of POMC was analyzed by western blot assay with an antiadrenocorticotropic hormone antibody (Abcam, Cambridge, UK).(30) The collected pituitary tissues were weighed and homogenized.”
MethodThe role of psychological stress in the pathogenesis of psoriasis
Lei, D., Gong, C., Wang, B., Zhang, L., Zhang, G., & Man, M. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1614863 · Cited by 12
Chen, W., Xu, Q., Xiao, Y., Zhou, J., Zhang, W., Lin, G., & Gong, F. (2016) · International Journal of Medical Sciences · doi:10.7150/ijms.17290 · Cited by 10
“The hypothalamic tissue specimens were fixed and stained by immunohistochemistry using rabbit anti-POMC precursor antibody (Abcam, Cambridge, UK) [16].”
MethodItoi‐Ochi, S., Terao, M., Murota, H., & Katayama, I. (2016) · Dermato-Endocrinology · doi:10.1080/19381980.2015.1119958 · Cited by 10
“It is reported that HPA axis also exists in the skin and synthesizes cortisol.(6,7,9-13) The skin is reported to have neuroendocrine capabilities that express elements of the HPA axis, key enzyme of corticosteroid glucocorticoids.”
BackgroundLee, S., Kim, S. Y., Lee, S., Jang, S., Hwang, S., Kwon, Y., Choi, J., & Kwon, O. (2024) · iScience · doi:10.1016/j.isci.2024.109675 · Cited by 9
“16,17 However, the cutaneous HPA axis shows differential susceptibility to ultraviolet radiation.”
Melanocortin therapies to resolve fibroblast-mediated diseases
Khodeneva, N., Sugimoto, M. A., Davan-Wetton, C. S. A., & Montero‐Melendez, T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1084394 · Cited by 10
Differential expression of proopiomelanocortin (POMC) transcriptional variants in human skin cells
Zapletal, E., Kraus, O., Čupić, B., & Gabrilovac, J. (2012) · Neuropeptides · doi:10.1016/j.npep.2012.10.010 · Cited by 9
“In this study we firstly intended to reproduce the data of Slominski et al. (2005a), i.e. to detect POMC transcripts in normal human keratinocytes and dermal fibroblasts by using probes, not distinguishing the full-length from the other POMC mRNA variants.”
InfluentialBéziers, P., Ducrest, A., San‐Jose, L. M., Simon, C., & Roulin, A. (2019) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2019.113224 · Cited by 8
Sevilla, L. M., Bigas, J., Chiner‐Oms, Á., Comas, I., Sentandreu, V., & Pérez, P. (2020) · Scientific Reports · doi:10.1038/s41598-020-75853-5 · Cited by 7
Watanuki, Y., Takayasu, S., Kageyama, K., Iwasaki, Y., Sakihara, S., Terui, K., Nigawara, T., & Suda, T. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.01.022 · Cited by 8
Soeberdt, M., Kilić, A., & Abels, C. (2020) · Experimental Dermatology · doi:10.1111/exd.14145 · Cited by 8
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_2 · Cited by 6
Effects of psychological stress on skin and hair pigmentation in Polish adolescents
Sitek, A., Żądzińska, E., & Rosset, I. (2012) · Anthropological Review · doi:10.2478/v10044-012-0001-7 · Cited by 6
“…hierarchical and conforms with classical organizational structures, such as the hypothalamic-pituitary-adrenal (HPA) axis (Slominski and Mihm 1996; Slominski et al. 2005c,d; 2007; Ito et al. 2005; Slominski 2009) as well as the sero toninergic (Slominski et al. 2005b) and catecholaminergic…”
Pondeljak, N., Lugović‐Mihić, L., Davidović, B. L., Karlović, D., Hanžek, M., & Neuberg, M. (2025) · Life · doi:10.3390/life15030351 · Cited by 5
Brain-Skin Connection: Impact of Psychological Stress on Skin
Chen, Y., Maidof, R., & Lyga, J. W. (2015) · Springer eBooks · doi:10.1007/978-3-642-27814-3_153-1 · Cited by 5
“Human melanocytes and dermal fibroblasts respond to CRH signaling via the cAMP pathway and lead to ACTH and corticosterone production [33, 34].”
Psoriasis and Stress – Psoriasis Aspect of Psychoneuroendocrinology
Zangeneh, F. Z., Fazeli, A., & Shooshtary, F. S. (2012) · InTech eBooks · doi:10.5772/25525 · Cited by 3
“, 2009) (Slominski et al., 2005) (Fig.”
Hormones and Hormone Precursors of the Skin
Kemény, L. V., & Fisher, D. E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813814-4.00023-7 · Cited by 3
Piñera-Moreno, R., Reyes‐López, F. E., Goldstein, M., Santillán-Araneda, M. J., Robles-Planells, B., Arancibia-Carvallo, C., Vallejos‐Vidal, E., Cuesta, A., Esteban, M. Á., & Tort, L. (2024) · Animals · doi:10.3390/ani14121815 · Cited by 2
Selective Vagotomy Worsens Glucose Control After Ileal Transposition
Chen, W., Xia, Z., Liu, W., He, X., & Zhang, W. (2018) · Obesity Surgery · doi:10.1007/s11695-018-3192-1 · Cited by 2
Feodora, I., Hostettler, N., Bianchi, P., & Brunner, T. (2012) · InTech eBooks · doi:10.5772/52788 · Cited by 2
“keratinocytes [66], melanocytes [13], dermal fibroblasts [67], immune cells and endothelial cells in the derma, as well as hair follicles [16] and skin tissue cultures, are able to respond to CRF stimulation and to produce proopiomelanocortin, which can be further processed into adrenocorticotropic hormone (ACTH), MSH…”
Brain-Skin Connection: Impact of Psychological Stress on Skin
Chen, Y., Maidof, R., & Lyga, J. W. (2016) · Springer eBooks · doi:10.1007/978-3-662-47398-6_153 · Cited by 2
Equivalent of Hypothalamo–Pituitary–Adrenal Axis in the Skin
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_7 · Cited by 1
Corticotropin Signaling System in the Skin
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_5 · Cited by 1
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.1600-0625.2006.00004.x · Cited by 1
Sun, M., & Rieder, E. A. (2021) · Wiley eBooks · doi:10.1002/9781119680116.ch1 · Cited by 1
(2005) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(05)00109-8 · Cited by 1
Corticotropin-Releasing Hormone (CRH)
Nicolaides, N. C., & Chrousos, G. P. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64324-6 · Cited by 1
Tobin, D. J., & Peters, E. M. J. (2009) · Springer eBooks · doi:10.1007/978-3-540-35989-0_13
RELATIONSHIP BETWEEN GENETIC MERIT AND BIOLOGICAL RESPONSE IN LACTATING COWS
Fanzago, M. (2015) · Institutional Research Information System (University of Udine)
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_6
Treatment of Diffuse Cutaneous Systemic Sclerosis with Hyperimmune Caprine Serum
Quillinan, N. (2016) · UCL Discovery (University College London)
Dlova, N. C., & Naidoo, L. (2017) · Springer eBooks · doi:10.1007/978-81-322-3664-1_10
Su, F., Xia, Y., Huang, M., Zhang, L., & Chen, L. (2018) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v16i11.4
“The tissue samples were used for isolation of RNA, quantification protein expression levels of CRH, CRHBP, IL-8 and IL33 as described previously [15,16].”
MethodKim, H. S., Cho, D. H., Kim, H. J., Lee, J. Y., Cho, B. K., & Park, H. J. (2006) · Experimental Dermatology · doi:10.1111/j.1600-0625.2006.00001.x
Su, F., Xia, Y., Huang, M., Zhang, L., & Chen, L. (2018) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v16i12.5
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.1600-0625.2006.00002.x
Young, M. J. (2007) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1089330.542550
Corticotropin-releasing hormone (CRH)
Nicolaides, N. C., Hatziagapiou, K., & Chrousos, G. P. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00315-0
Savic, D., Serafini, R. A., & Ning, S. (2026) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2026.101338
“Keratinocytes, melanocytes, fibroblasts, sebocytes, mast cells, and leukocytes can locally release CRH and POMC-derived peptides in response to stress, influencing cutaneous steroidogenic and immune signaling (Slominski et al., 2005, 2007).”
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
