Mechanisms of excessive estrogen formation in endometriosis.
Estrogen is produced in a number of human tissues including the ovary, placenta and extraglandular sites such as adipose tissue, skin and the brain. Aromatase is the key enzyme that regulates estrogen formation in these tissues. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by 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 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 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.
Bulun
Serdar E
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
Gurates
Bilgin
B
Fang
Zongjuan
Z
Tamura
Mitsutoshi
M
Sebastian
Siby
S
Zhou
Jianfeng
J
Amin
Sanober
S
Yang
Sijun
S
D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D047072:Aromatase Inhibitors; D004715:Endometriosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D012333:RNA, Messenger; D004958:Estradiol; D001141:Aromatase