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

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• 作者：Kaoruko Yamanaka ; M.D.^a ; Bing Xu ; M.D. ; Ph.D.^a ; Izumi Suganuma ; M.D.^a ; Izumi Kusuki ; M.D. ; Ph.D.^a ; Shizuka Mita ; M.S.^b ; Yutaka Shimizu ; Ph.D.^b ; Kiyoshi Mizuguchi ; Ph.D.^b ; Jo Kitawaki ; M.D. ; Ph.D.^a ; ^{kitawaki@koto.kpu-m.ac.jp}
• 关键词：Aromatase ; cyclooxygenase-2 ; dienogest ; endometriotic stromal cells ; spheroid culture
• 刊名：Fertility and Sterility
• 出版年：2012
• 出版时间：February, 2012
• 年：2012
• 卷：97
• 期：2
• 页码：477-482
• 全文大小：874 K

文摘

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Objective

To determine the effect of dienogest (DNG) on the expression of aromatase and cyclooxygenase-2 (COX-2) and the production of prostaglandin E₂ (PGE₂) 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 PGE₂ quantified by enzyme-linked immunosorbent assay (ELISA), and nuclear factor kappa B (NF-¦ÊB) 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 PGE₂ were examined using spheroid cultures of human ESCs. More aromatase, COX-2, and PGE₂ 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 PGE₂. DNG also inhibited NF-¦ÊB DNA-binding activity and reduced the immunocytochemical protein expression of aromatase, COX-2, and NF-¦ÊB p50 nuclear localization.

Conclusion(s)

Because DNG inhibits aromatase and COX-2 expression as well as PGE₂ production in ESCs, these pharmacologic features might contribute to a therapeutic effect of DNG on endometriosis.