Molecular basis for treating endometriosis with aromatase inhibitors.
Although treatment of one unusually aggressive case of postmenopausal endometriosis with an aromatase inhibitor has been strikingly successful, large clinical trials are required to establish whether aromatase inhibitors will have a significant role in the medical management of endometriosis. Introduction of aromatase inhibitors into the treatment of endometriosis underscores the importance of basic research leading to the development of novel strategies in reproductive disorders. It was shown earlier that aromatase activity was not detectable in normal endometrium. Aromatase, however, is expressed inappropriately in endometriosis and stimulated by prostaglandin E2. Aromatase activity gives rise to local biosynthesis of oestrogen, which, in turn, stimulates prostaglandin E2 production, thus establishing a positive feedback cycle. This favours accumulation of oestrogen and prostaglandins in endometriosis, which is an inflammatory disorder dependent on oestrogen for growth.
Bulun
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Department of Obstetrics and Gynecology, University of Illinois at Chicago, 60612, USA. sbulun@uic.edu
Zeitoun
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Takayama
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Sasano
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D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors; D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004715:Endometriosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression; D018398:Homeodomain Proteins; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000201:enzymology
D047072:Aromatase Inhibitors; D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D004967:Estrogens; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C497589:NR2F1 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D001141:Aromatase; D015232:Dinoprostone