The endocannabinoid 2-arachidonoylglycerol dysregulates the synthesis of proteins by the human syncytiotrophoblast

• Published in: Biochimica et biophysica acta Vol. 1861; no. 3; pp. 205 - 212
• Main Authors: Costa, M.A., Fonseca, B.M., Mendes, A., Braga, J., Teixeira, N.A., Correia-da-Silva, G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2016
• Subjects: 2-Arachidonoylglycerol; 3-Hydroxysteroid Dehydrogenases - biosynthesis; Arachidonic Acids - pharmacology; Aromatase - biosynthesis; Cannabinoid Receptor Agonists - pharmacology; Cells, Cultured; Chorionic Gonadotropin - biosynthesis; Cyclic AMP-Dependent Protein Kinases - metabolism; Dose-Response Relationship, Drug; Endocannabinoid signalling; Endocannabinoids - pharmacology; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Galectins - genetics; Galectins - metabolism; Glycerides - pharmacology; Human syncytiotrophoblast; Humans; Leptin - biosynthesis; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Placenta; Placental proteins; Pregnancy; Pregnancy Proteins - genetics; Pregnancy Proteins - metabolism; Protein Biosynthesis - drug effects; Signal Transduction - drug effects; Time Factors; Trophoblasts - drug effects; Trophoblasts - metabolism; 2-Arachidonoylglycerol; Placenta; Placental proteins; Endocannabinoid signalling; Human syncytiotrophoblast
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2015.12.008

In recent years, endocannabinoids emerged as new players in various reproductive events. Recently, we demonstrated the involvement of 2-arachidonoylglycerol (2-AG) in human cytotrophoblast apoptosis and syncytialization. However, 2-AG impact in hormone production by the syncytiotrophoblast (hST) was never studied. In this work, we demonstrate that 2-AG activates cannabinoid (CB) receptors, exerting an inhibitory action on cyclic AMP/protein kinase A (cAMP/PKA) and mitogen-activated protein kinase (MAPK) p38 pathways, and enhancing ERK 1/2 phosphorylation. Furthermore, 2-AG affects the synthesis of human chorionic gonadotropin (hCG), leptin, aromatase, 3-β-hydroxysteroid dehydrogenase (3-β-HSD), and placental protein 13 (PP13). These 2-AG effects are mediated by the activation of CB receptors, in a mechanism that may involve p38, ERK 1/2 and cAMP/PKA pathways, which participate in the regulation of placental proteins expression. To our knowledge, this is the first study that associates the endocannabinoid signalling and endocrine placental function, shedding light on a role for 2-AG in the complex network of molecules that orchestrate the production of placental proteins essential for the gestational success. •2-AG inhibits cAMP/PKA and p38 pathways and enhances ERK 1/2 pathways.•2-AG impairs protein synthesis by the human syncytiotrophoblast.•2-AG effects are mediated by the activation of cannabinoid receptors.•MAPK pathways regulate the transcription of important placental proteins.