Oxidative activity of the type 2 isozyme of 17β-hydroxysteroid dehydrogenase (17β-HSD) predominates in human sebaceous glands

Diane Thiboutot, Patricia Martin, Lazaros Volikos, Kathyrn Gilliland

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50 Scopus citations

Abstract

Sebum production is regulated by the opposing effects of androgens and estrogens. The intracrine activity of steroid metabolizing enzymes is important in regulating sebum production because these enzymes can convert weak steroids from the serum into potent androgens and estrogens within the sebaceous gland (SG). 17β-hydroxysteroid dehydrogenase (17β-HSD) interconverts weak and potent sex steroids via redox reactions. In this regard, it may function as a gatekeeping enzyme regulating the hormonal milieu of the SG. Six isozymes of 17β-HSD have been identified that differ in their substrate preference and their preference to produce weak or potent sex steroids via oxidation or reduction, respectively. The goals of this study are: (i) to identify which isozyme (s) of 17β-HSD is active in SG; (ii) to determine if its activity differs in facial skin compared with nonacne-prone skin that may account for the regional differences in sebum production; (iii) to compare the activity of 17β-HSD in intact glands and in SG homogenates; and (iv) to determine if 13-cis retinoic acid inhibits 17β- HSD activity. Human SG were assayed for 17β-HSD activity using estrogens, androgens, and progestins as substrates. Oxidative activity of the type 2 isozyme predominated in all samples tested. Although transcripts for the types 1, 2, 3, and 4 isozymes were detected using reverse transcriptase- polymerase chain reaction, only mRNA for the predominant type 2 isozyme and the type 4 isozyme were detected in northern analysis. Greater reductive activity of 17β-HSD was noted in SG from facial areas compared with nonacne- prone areas, suggesting an increased net production of potent androgens in facial areas. Oxidation was more predominant over reduction in intact SG compared with homogenized SG, thus supporting the hypothesis that 17β-HSD protects against the effects of potent androgens in vivo. Activity of the type 2 17β-HSD was not inhibited by 13-cis retinoic acid. In conclusion, SG possess the cellular machinery needed to transcribe the genes for the type 1- 4 isozymes of 17β-HSD. At the protein level, however, oxidative activity of the type 2 isozyme predominates, suggesting that 17β-HSD isozyme activity may be translationally regulated.

Original languageEnglish (US)
Pages (from-to)390-395
Number of pages6
JournalJournal of Investigative Dermatology
Volume111
Issue number3
DOIs
StatePublished - Sep 1998

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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