Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E₂ production in human endometriotic stromal cells in spheroid culture

Yamanaka K, Kaoruko Yamanaka, Bing Xu, Xu B, Suganuma I, Izumi Suganuma, Izumi Kusuki, Kusuki I, Mita S, Shizuka Mita, Shimizu Y, Yutaka Shimizu, Kiyoshi Mizuguchi, Mizuguchi K, Kitawaki J, Jo Kitawaki
Fertility and sterility · 2012 · vol. 97(2) , pp. 477–482 · doi:10.1016/j.fertnstert.2011.11.005 · PMID:22130322 · W2139847184
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Dienogest was found to decrease aromatase and cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic stromal cells grown in spheroid culture.

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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-κB) 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-κB DNA-binding activity and reduced the immunocytochemical protein expression of aromatase, COX-2, and NF-κB 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.

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Condition tags

endometriosis

MeSH descriptors

Aromatase Aromatase Inhibitors Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Dinoprostone Endometriosis Nandrolone Ovarian Diseases Ovary Stromal Cells Adult Adult Aromatase Aromatase Aromatase Aromatase Inhibitors Aromatase Inhibitors Cells, Cultured Cells, Cultured Cyclooxygenase 2

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