title: The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility.
abstract: BACKGROUND
  Marijuana, the most used recreational drug, has been shown to have adverse effects on human reproduction. Endogenous cannabinoids (also called endocannabinoids) bind to the same receptors as those of Δ(9)-tetrahydrocannabinol (THC), the psychoactive component of Cannabis sativa. The most extensively studied endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol. The endocannabinoids, their congeners and the cannabinoid receptors, together with the metabolic enzymes and putative transporters form the endocannabinoid system (ECS). In this review, we summarize current knowledge about the relationships of ECS, sex steroid hormones and cytokines in female fertility, and underline the importance of this endocannabinoid-hormone-cytokine network.
  
  
  METHODS
  Pubmed and the Web of Science databases were searched for studies published since 1985, looking into the ECS, sex hormones, type-1/2 T-helper (Th1/Th2) cytokines, leukaemia inhibitory factor, leptin and reproduction.
  
  
  RESULTS
  The ECS plays a pivotal role in human reproduction. The enzymes involved in the synthesis and degradation of endocannabinoids normalize levels of AEA for successful implantation. The AEA degrading enzyme (fatty acid amide hydrolase) activity as well as AEA content in blood may potentially be used for the monitoring of early pregnancies. Progesterone and oestrogen are involved in the maintenance of endocannabinoid levels. The ECS plays an important role in the immune regulation of human fertility.
  
  
  CONCLUSIONS
  The available studies suggest that tight control of the endocannabinoid-hormone-cytokine network is required for successful implantation and early pregnancy maintenance. This hormone-cytokine network is a key element at the maternal-foetal interface, and any defect in such a network may result in foetal loss.
authors.affiliation: Endocannabinoid Research Group (ERG), Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, PO Box 65, Leicester, Leicestershire LE2 7LX, UK.
authors.forename: T
authors.initials: T
authors.lastname: Karasu
authors.forename: T H
authors.initials: TH
authors.lastname: Marczylo
authors.forename: M
authors.initials: M
authors.lastname: Maccarrone
authors.forename: J C
authors.initials: JC
authors.lastname: Konje
mesh_terms: D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D063388:Endocannabinoids; D005260:Female; D005298:Fertility / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction
chemical_list: D063385:Cannabinoid Receptor Modulators; D016207:Cytokines; D063388:Endocannabinoids; D012739:Gonadal Steroid Hormones