Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance.
Conversion of C(19) steroids to estrogens is catalyzed by aromatase in human ovary, placenta and extraglandular tissues such as adipose tissue, skin and the brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by prostaglandin E(2) (PGE(2)).( )This results in local production of estrogen, which induces PGE(2) formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient hydroxysteroid dehydrogenase (17beta-HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE(2 )in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.
Departments of Obstetrics and Gynecology and Molecular Genetics, University of Illinois at Chicago, 820 S. Wood St. M/C 808, Illinois 60612, USA. sbulun@uic.edu
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Bulun
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Zeitoun
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Takayama
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Sasano
D000077384:Anastrozole; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D047072:Aromatase Inhibitors; D015232:Dinoprostone / Q000378:metabolism; D004715:Endometriosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004967:Estrogens / Q000096:biosynthesis*; D004970:Estrone / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009095:Mullerian Ducts / Q000201:enzymology; D009570:Nitriles / Q000627:therapeutic use; D011247:Pregnancy; D014230:Triazoles / Q000627:therapeutic use
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D000077384:Anastrozole; D001141:Aromatase; D015232:Dinoprostone