Role of aromatase in endometrial disease.
Aromatase is the key enzyme for estrogen biosynthesis. It is normally expressed in the human ovary, skin, adipose tissue and brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient 17beta-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 PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of post-menopausal endometriosis using an aromatase inhibitor.
Bulun
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SE
Department of Obstetrics and Gynecology, University of Illinois at Chicago, 820 S. Wood St. M/C 808, Chicago, IL 60612, USA. sbulun@uic.edu
Yang
S
S
Fang
Z
Z
Gurates
B
B
Tamura
M
M
Zhou
J
J
Sebastian
S
S
D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors; D015232:Dinoprostone / Q000378:metabolism; D004715:Endometriosis / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008954:Models, Biological; D009095:Mullerian Ducts / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D012333:RNA, Messenger; D004970:Estrone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D001141:Aromatase; D015232:Dinoprostone