title: Endocannabinoid regulation in human endometrium across the menstrual cycle.
abstract: Humans produce endogenous cannabinoids (endocannabinoids), a group of molecules that activate the same receptors as tetrahydrocannabinol. Endocannabinoids play important roles in reproduction in multiple species, but data in human endometrium are limited. Because endocannabinoids such as anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) often act within tissues as paracrine factors, their effects can be modulated by changes in expression of locally produced synthetic and degradative/oxidative enzymes. The objective of this study was to localize and quantify expression of these key synthetic and degradative/oxidative enzymes for AEA and 2-AG in human endometrium throughout the menstrual cycle. Key synthetic enzymes include N-arachidonyl-phosphatidylethanolamine phospholipase-D (NAPE-PLD), diacylglycerol-lipase a (DAGL-α, and DAGL-β. Key degradative enzymes include fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL); cyclooxygenase 2 (COX2) is an oxidative enzyme. Endometrial samples were collected in 49 regularly cycling, normal women. Protein localization and expression were achieved by immunohistochemistry and messenger RNA (mRNA) expression by real-time reverse transcriptase polymerase chain reaction. No significant cycle-dependent mRNA expression was observed except that of COX2 (P = .002), which demonstrated maximum expression in the proliferative phase. During the secretory phase, NAPE-PLD protein had increased expression in luminal (P = .001), stromal (P = .007), and glandular (P = .04) epithelia, while FAAH had increased glandular (P = .009) and luminal (P = .01) expression. Increased expression in glandular epithelia was identified for MAGL (P = .03). The COX2 had increased luminal expression during the early secretory phase (P < .0001). In conclusion, maximal expression of degradatory/oxidative enzymes in the secretory phase may foster decreased endocannabinoid tone during implantation.
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Jessica G
authors.initials: JG
authors.lastname: Scotchie
authors.affiliation: Departamento de Ginecologia e Obstetrícia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Savaris
authors.affiliation: Departamento de Ginecologia e Obstetrícia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Martin
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA steven_young@med.unc.edu.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Young
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008597:Menstrual Cycle / Q000378:metabolism*; D008994:Monoacylglycerol Lipases / Q000235:genetics / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D051546:Cyclooxygenase 2; D063388:Endocannabinoids; D005989:Glycerides; D008071:Lipoprotein Lipase; D008994:Monoacylglycerol Lipases; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C496540:PTGS2 protein, human; C480280:DAGLA protein, human; C480281:DAGLB protein, human; C581518:NAPEPLD protein, human; C078814:anandamide
keywords: cyclooxygenase 2; diacylglycerol-lipase; endometrium; fatty-acid amide hydrolase; monoacylglycerol lipase