Increased expression of type I 17beta-hydroxysteroid dehydrogenase enhances in situ production of estradiol in uterine leiomyoma.
Expression of 17beta-hydroxysteroid dehydrogenases (17beta-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 17beta-HSDs were then measured using real-time PCR techniques. Among the eight different types of 17beta-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 17beta-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 17beta-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 17beta-HSD, resulting in high conversion of estrone to estradiol. In situ expression of type 1 17beta-HSD may play a role in self-supported growth of leiomyoma cells.
Kasai
Tadayuki
T
Department of Obstetrics and Gynecology, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
Shozu
Makio
M
Murakami
Kouichi
K
Segawa
Tomoya
T
Shinohara
Kazunori
K
Nomura
Kazuhito
K
Inoue
Masaki
M
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000502:physiology*; D000328:Adult; D004958:Estradiol / Q000096:biosynthesis*; D004970:Estrone / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D014594:Uterine Neoplasms / Q000378:metabolism*
D012333:RNA, Messenger; D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases