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Sebocytes are the Key Regulators of Androgen Homeostasis in Human Skin
Open accessAbstract
The mRNA expression patterns of the androgen receptor and the androgen metabolizing enzymes 3beta-hydroxysteroid dehydrogenase/Delta(5-4)-isomerase, 17beta-hydroxysteroid dehydrogenase, 5alpha-reductase, and 3alpha-hydroxysteroid dehydrogenase were investigated in three different cell populations originating from human skin, SZ95 sebocytes, HaCaT keratinocytes, and MeWo melanoma cells, by means of reverse transcription polymerase chain reaction. Restriction analysis of cDNA fragments was performed to identify isozymes of 3beta-hydroxysteroid dehydrogenase/Delta(5-4)-isomerase and 3alpha-hydroxysteroid dehydrogenase. In addition, 3H-dihydroepiandrosterone and 3H-testosterone were used as substrates to determine the metabolic activity of these enzymes in SZ95 sebocytes, primary sebocyte cultures, and HaCaT keratinocytes. Furthermore, the effects of the selective 5alpha-reductase type 1 and 2 inhibitors, 4,7beta-dimethyl-4-aza-5alpha-cholestan-3-one and dihydrofinasteride, respectively, and of the 3beta-hydroxysteroid dehydrogenase/Delta(5-4)-isomerase inhibitor cyproterone acetate on androgen metabolism were investigated. Androgen receptor mRNA was detected in SZ95 sebocytes and HaCaT keratinocytes but not in MeWo melanoma cells, whereas 3beta-hydroxysteroid dehydrogenase/Delta(5-4)-isomerase isotype 1 mRNA and metabolic activity were only found in SZ95 sebocytes. The enzyme activity could be inhibited by cyproterone acetate. Type 2 17beta-hydroxysteroid dehydrogenase, type 1 5alpha-reductase, and 3alpha-hydroxysteroid dehydrogenase mRNA were expressed in all three cell populations tested, whereas type 3 17beta-hydroxysteroid dehydrogenase mRNA could only be detected in SZ95 sebocytes. The major metabolic steps of testosterone in SZ95 sebocytes, primary sebocyte cultures, and HaCaT keratinocytes were its conversion to androstenedione by 17beta-hydroxysteroid dehydrogenase and further to 5alpha-androstanedione by 5alpha-reductase. The type 1 5alpha-reductase selective inhibitor 4,7beta-dimethyl-4-aza-5alpha-cholestan-3-one, but not the type 2 selective inhibitor dihydrofinasteride, inhibited 5alpha-reductase at low concentrations in SZ95 sebocytes and HaCaT keratinocytes. 5alpha-androstanedione was degraded to androsterone by 3alpha-hydroxysteroid dehydrogenase, which exhibited a stronger activity in HaCaT keratinocytes than in SZ95 sebocytes and in primary sebocyte cultures. Lower levels of 5alpha-dihydrotestosterone and 5alpha-androstanediol were also detected in all cells tested. Our investigations show that specific enzyme expression and activity in cultured sebocytes and keratinocytes seem to allocate different duties to these cells in vitro. Sebocytes are able to synthesize testosterone from adrenal precursors and to inactivate it in order to maintain androgen homeostasis, whereas keratinocytes are responsible for androgen degradation.
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“A prominent androgen is 5α-dihydrotestosterone (5α-DHT), as sebocytes are able to convert testosterone to 5α-DHT with the enzyme 5α-reductase type I68.”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [68]
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In the citing paper
“Both testosterone and 5α-DHT increase sebaceous proliferation, however, they do not affect lipid synthesis.68,69”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [68]
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In the citing paper
“Both testosterone and 5α-DHT increase sebaceous proliferation, however, they do not affect lipid synthesis.68,69”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [68]
Experimental — accuracy not yet measuredIn the citing paper
“Greater activity of the 17βHSD types 3 and 5 was detected in sebaceous glands of facial skin than in other, non-acne prone skin areas, suggesting the in situ more potent androgen formation in these areas [74, 101].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [101]
In the citing paper
“Functional comparison of different epidermal cell types hint at differential functions for androgen biosynthesis and inactivation (Fritsch et al., 2001).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Fritsch et al., 2001
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Metadata
- Authors
- Fritsch, M., Orfanos, C. E., & Zouboulis, C. C.
- Affiliations
- Freie Universität Berlin (DE)
- Corresponding author
- Zouboulis, Christos C.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 116
- Issue
- 5
- Pages
- 793-800
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2094557019
- Cited by
- 232
- References
- 61
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 14 · 2021: 8 · 2020: 6 · 2019: 12 · 2018: 8 · 2017: 15 · 2016: 4 · 2015: 14 · 2014: 19 · 2013: 8 · 2012: 8
- FWCI
- 12.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
- Health Sciences › Medicine › Dermatology › Hair Growth and Disorders
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- sebocytes, androgen receptor, 17β-hydroxysteroid dehydrogenase, 5α-reductase, 3α-hydroxysteroid dehydrogenase, testosterone metabolism, dihydrotestosterone, androstenedione, cyproterone acetate
- MeSH terms
- Androgens, Cell Line, Dehydroepiandrosterone, Enzyme Inhibitors, Homeostasis, Humans, Hydroxysteroid Dehydrogenases, Oxidoreductases, Receptors, Androgen, RNA, Messenger, Sebum, Skin Physiological Phenomena, Testosterone, Cyproterone Acetate, Reverse Transcriptase Polymerase Chain Reaction, Cholestenone 5 alpha-Reductase
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