Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target.
OBJECTIVE
To provide a clinically useful model illustrating the molecular aberrations affecting estrogen biosynthesis and metabolism in endometriosis and to discuss the therapeutic role of aromatase inhibitors.


METHODS
Literature review.


RESULTS
Several molecular aberrations were found in endometriotic lesions (in contrast to eutopic endometrium) that favor increased local concentrations of E2. Endometriotic stromal cells aberrantly express aromatase, which converts C19, steroids to estrogens. Aromatase activity in these cells is stimulated by prostaglandin (PG)E2. Estrogen stimulates cyclooxygenase-2, giving rise to increased PGE2 formation. Thus, this positive feedback loop produces increasing quantities of E2 and PGE2 in endometriosis. The lack of aromatase expression in eutopic endometrium is maintained by binding of an inhibitory transcription factor, COUP-TF, to the aromatase promoter. In endometriosis, however, an aberrantly expressed factor, SF-1, displaces COUP-TF to bind to this same promoter and activates aromatase expression and thus local estrogen biosynthesis. Additionally, endometriotic glandular cells are deficient in 17beta-hydroxysteroid dehydrogenase type 2, which converts E2 to estrone in the eutopic endometrium in response to P. Deficiency of this enzyme in endometriosis impairs the inactivation of E2 and may be a consequence of insensitivity to P.


CONCLUSIONS
Molecular aberrations that increase local E2 concentrations may be important in the etiology of endometriosis. These molecules may be targeted to develop novel therapeutic strategies. The clinical relevance of aromatase expression in endometriosis was shown recently by the successful treatment of an unusually aggressive case of postmenopausal endometriosis with use of an aromatase inhibitor.
Zeitoun
K M
KM
Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center, Dallas, USA.
Bulun
S E
SE
D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors; D004715:Endometriosis / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D004717:Endometrium / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000502:physiology; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D017154:Stromal Cells / Q000201:enzymology
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D001141:Aromatase