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

Capsule:
Dienogest inhibits aromatase expression and PGE2 production by inhibiting COX-2 expression in spheroid cultures of endometriotic cells. These features might contribute to a therapeutic effect of dienogest upon endometriosis.

Authors:
Kaoruko Yamanaka, M.D., Bing Xu, M.D., Ph.D., Izumi Suganuma, M.D., Izumi Kusuki, M.D., Ph.D., Shizuka Mita, M.S., Yutaka Shimizu, Ph.D., Kiyoshi Mizuguchi, Ph.D., Jo Kitawaki, M.D., Ph.D.
Volume 97, Issue 2 , Pages 477-482, February 2012

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-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 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-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 PGE2 production in ESCs, these pharmacologic features might contribute to a therapeutic effect of DNG on endometriosis.

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