Cannabinoid receptor I activation markedly inhibits human decidualization

Cherie A. Kessler, Kenneth K. Moghadam, Jennifer K. Schroeder, Arthur R. Buckley, Anoop K. Brar, Stuart Handwerger

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The role of cannabinoid receptor I (CBR-1) in the induction of decidualization was examined using decidual fibroblasts and human endometrial stromal cells as model systems. Decidual fibroblasts decidualized in vitro for 3 and 6 days in the presence of the CBR-1 agonist R(+)-WIN 55,212-2 mesylate (WIN, 0.1-10 μM) expressed less of the decidualization-specific markers prolactin, CBR-1, forkhead (FKHR), TIMP-3, laminin, endometrial bleeding associated factor (EBAF), decorin and insulin-like growth factor binding protein-1 (IGFBP-1) mRNA levels compared to control cells. The maximal decrease for each transcript was in the range of 50-99%. In contrast, cells exposed to the CBR-1 inhibitor AM-251 (1 μM) expressed about two-fold higher levels of the decidualization-specific marker gene mRNAs. The WIN-exposed cells showed a marked decrease in intracellular cAMP levels and a progressive, concentration-dependent increase in DNA fragmentation (TUNEL assay) and caspase 3 levels during decidualization compared to control cells. These studies strongly suggest that activation of CBR-1 inhibits human decidualization and stimulates apoptosis by a cAMP-dependent mechanism.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume229
Issue number1-2
DOIs
StatePublished - Jan 14 2005
Externally publishedYes

Keywords

  • Cannabinoid receptor
  • Decidualization
  • Pregnancy
  • Uterus

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    Kessler, C. A., Moghadam, K. K., Schroeder, J. K., Buckley, A. R., Brar, A. K., & Handwerger, S. (2005). Cannabinoid receptor I activation markedly inhibits human decidualization. Molecular and Cellular Endocrinology, 229(1-2), 65-74. https://doi.org/10.1016/j.mce.2004.09.007