Down-regulation of anandamide hydrolase in mouse uterus by sex hormones

Mauro Maccarrone, Massimo De Felici, Monica Bari, Francesca Klinger, Gregorio Siracusa, Alessandro Finazzi-Agrò

Research output: Contribution to journalArticlepeer-review

Abstract

Endocannabinoids are an emerging class of lipid mediators, which mimic several effects of cannabinoids. Anandamide (arachidonoylethanolamide) is a major endocannabinoid, which has been shown to impair pregnancy and embryo development. The activity of anandamide is controlled by cellular uptake through a specific transporter and intracellular degradation by the enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH). We characterized FAAH in mouse uterus by radiochromatographic and immunochemical techniques, showing that the enzyme is confined to the epithelium and its activity decreases appreciably during pregnancy or pseudopregnancy because of lower gene expression at the translational level. Ovariectomy prevented the decrease in FAAH, and both progesterone and estrogen further reduced its basal levels, suggesting hormonal control of the enzyme. Anandamide was shown to induce programmed cell death in mouse blastocysts, through a pathway independent of type-1 cannabinoid receptor. Blastocysts, however, have a specific anandamide transporter and FAAH, which scavenge this lipid. Taken together, these results provide evidence of an interplay between endocannabinoids and sex hormones in pregnancy. These findings may also be relevant for human fertility, as epithelial cells from healthy human uterus showed FAAH activity and expression, which in adenocarcinoma cells was increased fivefold.

Original languageEnglish
Pages (from-to)2991-2997
Number of pages7
JournalEuropean Journal of Biochemistry
Volume267
Issue number10
DOIs
Publication statusPublished - 2000

Keywords

  • Anandamide hydrolase
  • Apoptosis
  • Development
  • Endocannabinoids
  • Sex hormones

ASJC Scopus subject areas

  • Biochemistry

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