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Increased Expression of Type I 17ß-Hydroxysteroid Dehydrogenase Enhances in Situ Production of Estradiol in Uterine Leiomyoma

Department of Obstetrics and Gynecology, Kanazawa University School of Medicine, Kanazawa 920-0934, Japan

Address all correspondence and requests for reprints to: Makio Shozu, M.D., Department of Obstetrics and Gynecology, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa 920-0934, Japan. E-mail: shozu{at}med.kanazawa-u.ac.jp.

Expression of 17ß-hydroxysteroid dehydrogenases (17ß-HSDs) was compared between leiomyoma and myometrium. Cytosolic fractions from leiomyoma homogenate displayed 5-fold higher activity (estrone to estradiol), compared with surrounding myometrium (n = 6, P < 0.05), whereas microsomal fractions showed no difference. Oxidative activity (estradiol to estrone) did not differ between leiomyoma and myometrium. Levels of mRNA for 17ß-HSDs were then measured using real-time PCR techniques. Among the eight different types of 17ß-HSDs (types 1–5, 7, 8, and 10), type 1 was the only enzyme displaying differential expression between leiomyoma and myometrium. Mean concentration of type 1 17ß-HSD mRNA was 4-fold higher in leiomyoma than in surrounding myometrium (n = 20, P < 0.05). Type 1 transcript levels correlated significantly with reductive activity in individual samples (n = 6, P < 0.05). Northern blot analysis of leiomyoma and myometrium tissues detected 2.3- and 1.0-kb transcripts of type 1 enzyme, whereas the major 1.3-kb transcript for 17ß-HSD in placenta-derived JEG-3 cells was not detected. None of the factors increasing mRNA levels for type 1 enzyme in placenta increased mRNA levels in leiomyoma.

These results indicate that leiomyoma tissues overexpress type 1 17ß-HSD, resulting in high conversion of estrone to estradiol. In situ expression of type 1 17ß-HSD may play a role in self-supported growth of leiomyoma cells.

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