title: The endocannabinoid 2-arachidonoylglycerol dysregulates the synthesis of proteins by the human syncytiotrophoblast.
abstract: 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.
authors.affiliation: Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors.forename: M A
authors.initials: MA
authors.lastname: Costa
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors.forename: B M
authors.initials: BM
authors.lastname: Fonseca
authors.affiliation: Departamento da Mulher e da Criança, Serviço de Obstetrícia, Centro Materno-Infantil do Norte-Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Mendes
authors.affiliation: Departamento da Mulher e da Criança, Serviço de Obstetrícia, Centro Materno-Infantil do Norte-Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Braga
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors.forename: N A
authors.initials: NA
authors.lastname: Teixeira
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic address: george@ff.up.pt.
authors.forename: G
authors.initials: G
authors.lastname: Correia-da-Silva
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis; D001095:Arachidonic Acids / Q000494:pharmacology*; D001141:Aromatase / Q000096:biosynthesis; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D037161:Galectins / Q000235:genetics / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D020738:Leptin / Q000096:biosynthesis; D010766:Phosphorylation; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D006063:Chorionic Gonadotropin; D063388:Endocannabinoids; D037161:Galectins; D005989:Glycerides; C038195:LGALS13 protein, human; D020738:Leptin; D011257:Pregnancy Proteins; C094503:glyceryl 2-arachidonate; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; C561410:CYP19A1 protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 2-Arachidonoylglycerol; Endocannabinoid signalling; Human syncytiotrophoblast; Placenta; Placental proteins