Steroidogenic factor-1 and endometriosis.
Endometriosis is a common and chronic disease characterized by persistent pelvic pain and infertility. Estradiol is essential for growth and inflammation in endometriotic tissue. The complete cascade of steroidogenic proteins/enzymes including aromatase is present in endometriosis leading to de novo estradiol synthesis. PGE(2) induces the expression of the genes that encode these enzymes. Upon PGE(2) treatment, coordinate recruitment of the nuclear receptor SF-1 to the promoters of these steroidogenic genes is the key event for estradiol synthesis. SF-1 is the key factor determining that an endometriotic cell will respond to PGE(2) by increased estradiol formation. The presence of SF-1 in endometriosis and its absence in endometrium is determined primarily by the methylation of its promoter. The key steroidogenic enzyme in endometriosis is aromatase encoded by a single gene because its inhibition blocks all estradiol biosynthesis. Aromatase inhibitors diminish endometriotic implants and associated pain refractory to existing treatments in affected women.
Bulun
Serdar E
SE
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, 333 E. Superior Street, Suite 484, Chicago, IL 60611, United States. s-bulun@northwestern.edu
Utsunomiya
Hiroki
H
Lin
Zhihong
Z
Yin
Ping
P
Cheng
You-Hong
YH
Pavone
Mary E
ME
Tokunaga
Hideki
H
Trukhacheva
Elena
E
Attar
Erkut
E
Gurates
Bilgin
B
Milad
Magdy P
MP
Confino
Edmond
E
Su
Emily
E
Reierstad
Scott
S
Xue
Qing
Q
D015232:Dinoprostone / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D004958:Estradiol; D015232:Dinoprostone