Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E(2) production in human endometriotic stromal cells in spheroid culture.
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Yamanaka K, Xu B, Suganuma I, Kusuki I, Mita S, Shimizu Y, Mizuguchi K, Kitawaki J
Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E(2) production in human endometriotic stromal cells in spheroid culture.
Fertil Steril. 2012 Feb;97(2):477-82. doi: 10.1016/j.fertnstert.2011.11.005. Epub 2011 Nov 30.
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- 22130322 [ View in PubMed]
- Abstract
OBJECTIVE: To determine the effect of dienogest (DNG) on the expression of aromatase and cyclooxygenase-2 (COX-2) and the production of prostaglandin E(2) (PGE(2)) in human endometriotic stromal cells (ESCs). DESIGN: Experimental study in vitro. SETTING: University hospital. PATIENT(S): Seventeen patients with ovarian endometrioma. INTERVENTION(S): ESCs from chocolate cyst linings of ovaries were treated with DNG. MAIN OUTCOME MEASURE(S): Expression of aromatase and COX-2 evaluated in spheroid cultures of human ESCs by real-time quantitative polymerase chain-reaction and immunocytochemistry, production of PGE(2) quantified by enzyme-linked immunosorbent assay (ELISA), and nuclear factor kappa B (NF-kappaB) DNA-binding examined by ELISA and immunocytochemistry. RESULT(S): The pharmaceutical actions of DNG on the expression of aromatase and COX-2 and the production of PGE(2) were examined using spheroid cultures of human ESCs. More aromatase, COX-2, and PGE(2) were expressed in spheroid cultures than in conventional ESCs monolayers. In the spheroid cultures, DNG (10(-7) M) and progesterone (10(-7) M) inhibited the expression of aromatase, COX-2, and PGE(2). DNG also inhibited NF-kappaB DNA-binding activity and reduced the immunocytochemical protein expression of aromatase, COX-2, and NF-kappaB p50 nuclear localization. CONCLUSION(S): Because DNG inhibits aromatase and COX-2 expression as well as PGE(2) production in ESCs, these pharmacologic features might contribute to a therapeutic effect of DNG on endometriosis.