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

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.

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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



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).


Experimental study in vitro.


University hospital.


Seventeen patients with ovarian endometrioma.


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.


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.


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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(11)02759-2/fulltext

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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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