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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Cortisol and corticosterone production was detected in epidermal melanocytes and dermal fibroblasts, with chemical structure confirmed by LC/MS.
“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 skin, induction of steroidogenesis by CRH, ACTH, or factors raising intracellular cAMP is cell type dependent: corticosterone and cortisol formation is induced in normal and malignant epidermal melanocytes and dermal fibroblasts, but not in epidermal keratinocytes.
“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]
Steroid production in skin after CRH stimulation is strongly dependent on the CRH-R1 receptor.
“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]
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- 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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