title: The endocannabinoid system in the human granulosa cell line KGN.
abstract: Ovarian steroidogenesis is embedded in a sensitive network of regulatory mechanisms crucial for human fertility. The endocannabinoid system (ECS) represents an intrinsic modulating system involved in the regulation of endocrine functions. In the present study we characterized the ECS in the human granulosa cell line KGN and its impact on gonadotropin sensitivity and steroid hormone synthesis under basal and FSH-stimulated conditions. Expression studies were performed and estradiol was measured. CB1, CB2, DAGL, FAAH, GPR55, MAGL, NAPE-PLD and TRPV1 were expressed without FSH-dependent effects. Treatment with selective cannabinoid receptor agonists reduced basal but not FSH-stimulated estradiol and CYP19. Progesterone was not altered by ECS manipulation. CB1 agonist changed the expression of miRNAs associated with granulosa cell function, e.g. miR-23a, miR-24, miR-181a and miR-320a. Present data indicate a modulating role of the intrinsic ovarian ECS in the regulation of estradiol synthesis.
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle (Saale), Germany. Electronic address: jana.ernst@medizin.uni-halle.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Ernst
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle (Saale), Germany.
authors.forename: Urszula
authors.initials: U
authors.lastname: Grabiec
authors.affiliation: Center for Reproductive Medicine and Andrology, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06120 Halle (Saale), Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Greither
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle (Saale), Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Fischer
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle (Saale), Germany.
authors.forename: Faramarz
authors.initials: F
authors.lastname: Dehghani
mesh_terms: D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology; D002460:Cell Line; D063388:Endocannabinoids / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology / Q000502:physiology; D015870:Gene Expression; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D015398:Signal Transduction; D013799:Theca Cells / Q000378:metabolism
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D063388:Endocannabinoids; D007211:Indoles; D035683:MicroRNAs; D009025:Morpholines; D011720:Pyrazoles; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; C109925:AM 281; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; C094023:iodopravadoline
keywords: Endocannabinoid system; Estradiol; Granulosa cells; KGN; miRNA