title: Expression and function of OXE receptor, an eicosanoid receptor, in steroidogenic cells.
abstract: Hormonal regulation of steroidogenesis involves arachidonic acid (AA) metabolism through the 5-lipoxygenase pathway. One of the products, 5-hydroperoxy-eicosatetraenoic acid (5-HpETE), acts as a modulator of the activity of the steroidogenic acute regulatory (StAR) protein promoter. Besides, an oxoeicosanoid receptor of the leukotriene receptor family named OXE-R is a membrane protein with high affinity and response to 5-HpETE, among other AA derivatives. The aim of our work was to elucidate whether this receptor may be involved in steroidogenesis. RT-PCR and western blot analysis demonstrated the presence of the mRNA and protein of the receptor in human H295R adrenocortical cells. The treatment of H295R or MA-10 cells (murine Leydig cell line) with 8Br-cAMP together with docosahexaenoic acid (DHA, an antagonist of the receptor) partially reduced StAR induction and steroidogenesis. On the contrary, 5-oxo-ETE - the prototypical agonist, with higher affinity and potency on the receptor - increased cAMP-dependent steroid production, StAR mRNA and protein levels. These results lead us to conclude that AA might modulate StAR induction and steroidogenesis, at least in part, through 5-HpETE production and activation of a membrane receptor, such as the OXE-R.
authors.affiliation: INBIOMED - UBA/CONICET, Department of Biochemistry, School of Medicine, University of Buenos Aires, Paraguay 2155, C1121ABG Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Cooke
authors.forename: Hernán
authors.initials: H
authors.lastname: Di Cónsoli
authors.forename: Paula
authors.initials: P
authors.lastname: Maloberti
authors.forename: Fabiana
authors.initials: F
authors.lastname: Cornejo Maciel
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001095:Arachidonic Acids / Q000494:pharmacology; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D018055:Receptors, Eicosanoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013256:Steroids / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D001095:Arachidonic Acids; D015289:Leukotrienes; C504018:OXER1 protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D018055:Receptors, Eicosanoid; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C025348:arachidonic acid 5-hydroperoxide