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Cited by 43Hormonal and reproductive studiesHair Growth and DisordersSteroid Chemistry and Biochemistry

Epidermal Keratinocytes: A Source of 5α- Dihydrotestosterone Production in Human Skin*

MILEWICH, LEON, KAIMAL, VALSALA, SHAW, CYNTHIA B., SONTHEIMER, RICHARD D.·1986·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem-62-4-739
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Abstract

The major products of testosterone, androstenedione, and progesterone metabolism by human epidermal keratinocytes are 5 alpha-reduced steroids, viz. 5 alpha-dihydrotestosterone, 5 alpha-androstanedione, and 5 alpha-dihydroprogesterone, respectively. The rates of metabolite formation by these cells were linear with incubation time up to 3 h. The apparent Km of keratinocyte 5 alpha-reductase was 1.3 microM for androstenedione and 1.5 microM for progesterone. 5 alpha-Reductase activity was found only in particulate subcellular fractions of a homogenate of epidermal keratinocytes when assayed with tritium-labeled progesterone as the substrate and NADPH as the cofactor. In addition to 5 alpha-reductase activity, other enzymatic activities found in epidermal keratinocytes were 17 beta-hydroxysteroid oxidoreductase and 3 beta-hydroxysteroid oxidoreductase. These enzymes were expressed in the formation of androstenedione from testosterone, testosterone from androstenedione, isoandrosterone from androstenedione, and 3 beta-hydroxy-5 alpha-pregnan-20-one from progesterone. The apparent Km of 17 beta-hydroxysteroid oxidoreductase for androstenedione in epidermal keratinocytes was 10 microM. When measured at weekly intervals, the rates of product formation from testosterone, androstenedione, or progesterone by cultured epidermal keratinocytes increased several-fold with advancing time in culture up to 3 weeks. The results of these studies suggest that epidermal keratinocytes are a major site of synthesis of biologically potent androgens in human skin, viz. testosterone from androstenedione and 5 alpha-dihydrotestosterone from testosterone. Skin is a target organ for 5 alpha-dihydrotestosterone action, and thus, the local formation of 5 alpha-dihydrotestosterone may play an important role in the regulation of proliferation and differentiation of keratinocytes.

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  • The low rate of cutaneous steroid production can explain why earlier studies did not detect cortisol formation by keratinocytes.

    “This low rate of production could explain the lack of detection of cortisol formation by keratinocytes in earlier studies by Milevich et al. [78] and later by us [79].”

    From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [78]

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Authors
MILEWICH, L., KAIMAL, V., SHAW, C. B., & SONTHEIMER, R. D.
Affiliations
The University of Texas Southwestern Medical Center (US)
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1986-04
Volume
62
Issue
4
Pages
739-746
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem-62-4-739
OpenAlex
W2119891164
Cited by
43
References
26
Citations by year
2023: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2013: 1 · 2012: 4
FWCI
0.91
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01am019101-09, AM27257)
  • National Institute of Allergy and Infectious Diseases (AI17363)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
Keywords
epidermal keratinocytes, dihydrotestosterone, 5α-reductase, steroidogenesis, androgen production, androstenedione, progesterone metabolism, 17β-hydroxysteroid dehydrogenase, keratinocyte proliferation and differentiation, enzyme subcellular localization
MeSH terms
Adult, Androstenedione, Breast, Chromatography, Female, Humans, Kinetics, Male, Middle Aged, Progesterone, Skin, Dihydrotestosterone, Subcellular Fractions, Testosterone, Thigh, In Vitro Techniques

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