Chlormadinone acetate suppresses prostaglandin biosynthesis in human endometrial explants

Chlormadinone acetate down-regulated cyclo-oxygenase-2 messenger RNA expression and suppressed prostaglandin F2a production ex vivo in an interleukin-1b–stimulated human endometrial explants model, whereas the glucocorticoid reference compound dexamethasone showed no effect.

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Authors

Aida Hanjalic-Beck, M.D., Wolfgang R. Schäfer, Ph.D., Wolfgang R. Deppert, Ph.D., Lara Fischer, Antonia Stein, Laura Seebacher, M.D., Akou Seli von Gradowski, Johanna Stuckenschneider, Hans P. Zahradnik, M.D.

Vol 98, Issue 4, Pages 1017-1022

Abstract

Objective:

To elucidate the mode of action of chlormadinone acetate (CMA) in reducing dysmenorrheic pain, we studied the effects of CMA and dexamethasone (DEX) on mRNA abundance of cyclooxygenase-2 (COX-2), annexin-1 (ANXA1), glucocorticoid receptor (GR), progesterone receptor (PR) and concentrations of prostaglandin F2α (PGF2α) and leukotrienes B4 (LTB4) and C4 (LTC4) in human endometrial explants.

Design:

Ex vivo study.

Setting:

University hospital.

Patients:

Fifteen premenopausal patients undergoing surgery for benign gynaecological disorders.

Intervention:

Endometrial explants were obtained by aspiration curettage and stimulated ex vivo with IL-1β before exposure to CMA or DEX, mRNA levels were determined via reverse transcription quantitative real-time PCR (RT-qPCR) and concentrations of arachidonic acid metabolites by enzyme immunoassays.

Main Outcome Measures:

Messenger RNA levels of COX-2, ANXA1, PR, and GR; concentrations of PGF2α, LTB4, and LTC4 in endometrial explants treated with CMA or DEX.

Results:

In IL-1ß-treated explants COX-2 mRNA and PGF2α concentrations were significantly down-regulated by CMA, but not by DEX. CMA did not affect mRNA abundance of ANXA1, PR and GR.

Conclusions:

Our data suggest that CMA is a suppressor of COX-2 expression. Comparison with DEX revealed that progestin specific activity of CMA may mainly be responsible for suppression of prostaglandin biosynthesis in human endometrium.

Read the full text at: http://www.fertstert.org/article/S0015-0282(12)00645-0/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

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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