Aromatase and endometriosis.
Aromatase p450 (p450arom) is the key enzyme for biosynthesis of estrogen, which is an essential hormone for the establishment and growth of endometriosis. There is no detectable aromatase enzyme activity in normal endometrium; therefore, estrogen is not locally produced in endometrium. Endometriosis tissue, however, contains very high levels of aromatase enzyme, which leads to production of significant quantities of estrogen. Moreover, one of the best-known mediators of inflammation and pain, prostaglandin E (2), strikingly induces aromatase enzyme activity and formation of local estrogen in this tissue. Additionally, estrogen itself stimulates cyclo-oxygenase-2 and therefore increases the formation of prostaglandin E (2) in endometriosis. We were able to target this positive feedback cycle in endometriosis using aromatase inhibitors. In fact, pilot trials showed that aromatase inhibitors could decrease pelvic pain associated with endometriosis.
Bulun
Serdar E
SE
Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois 60611, USA.
Fang
Zongjuan
Z
Imir
Gonca
G
Gurates
Bilgin
B
Tamura
Mitsutoshi
M
Yilmaz
Bertan
B
Langoi
David
D
Amin
Sanober
S
Yang
Sijun
S
Deb
Santanu
S
D001141:Aromatase / Q000378:metabolism*; D004715:Endometriosis / Q000188:drug therapy / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017154:Stromal Cells / Q000201:enzymology
D004791:Enzyme Inhibitors; D004967:Estrogens; D001141:Aromatase