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Cited by 232Acne and Rosacea Treatments and EffectsHair Growth and DisordersDermatology and Skin Diseases

Sebocytes are the key regulators of androgen homeostasis in human skin

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Fritsch, Martin, Orfanos, Constantin E., Zouboulis, Christos C.·2001·Journal of Investigative Dermatology
DOI 10.1046/j.1523-1747.2001.01312.x
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Abstract

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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  • Sebocytes are able to convert testosterone to 5α-dihydrotestosterone (5α-DHT) with the enzyme 5α-reductase type I.

    “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]

  • Testosterone and 5α-DHT do not affect lipid synthesis.

    “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]

    The paper discusses androgen metabolism in sebocytes and says testosterone stimulates sebum secretion in humans (opening text labeled Abstract; page unavailable). Neither that passage nor the passages found by searching for lipid synthesis and lipid address whether testosterone or 5α-DHT affects lipid synthesis; sebum secretion is not the same measurement. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

  • Both testosterone and 5α-DHT increase sebaceous proliferation.

    “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]

    The introductory passage (p. 793) reports that testosterone stimulates sebum secretion, not sebaceous proliferation. The testosterone-metabolism results and Discussion (pp. 793–800) address conversion to 5α-DHT but do not report whether either androgen increases sebaceous proliferation. Searches for proliferation and cell growth found no passage establishing the claim. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Greater activity of 17βHSD types 3 and 5 in facial sebaceous glands than in non-acne-prone areas suggests more potent in situ androgen formation in facial skin.

    “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]

  • Functional comparison of different epidermal cell types hints at differential functions for androgen biosynthesis and inactivation.

    “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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Authors
Fritsch, M., Orfanos, C. E., & Zouboulis, C. C.
Affiliations
Freie Universität Berlin (DE)
Corresponding author
Zouboulis, Christos C.
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2001-05
Volume
116
Issue
5
Pages
793-800
ISSN
0022-202X (ISSN-L)
DOI
10.1046/j.1523-1747.2001.01312.x
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
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
  • Health Sciences › Medicine › Urology › 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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