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

Fertil Steril. 2012 Feb;97(2):477-82. doi: 10.1016/j.fertnstert.2011.11.005. Epub 2011 Nov 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aromatase / genetics
  • Aromatase / metabolism*
  • Aromatase Inhibitors / pharmacology*
  • Cells, Cultured
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • DNA / metabolism
  • Dinoprostone / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endometriosis / enzymology*
  • Endometriosis / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Immunohistochemistry
  • NF-kappa B / metabolism
  • Nandrolone / analogs & derivatives*
  • Nandrolone / pharmacology
  • Ovarian Diseases / enzymology*
  • Ovarian Diseases / genetics
  • Ovary / drug effects*
  • Ovary / enzymology
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Spheroids, Cellular
  • Stromal Cells / drug effects*
  • Stromal Cells / enzymology
  • Young Adult

Substances

  • Aromatase Inhibitors
  • Cyclooxygenase 2 Inhibitors
  • NF-kappa B
  • RNA, Messenger
  • dienogest
  • Nandrolone
  • DNA
  • Aromatase
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Dinoprostone