title: Parallel regulation of thyroid hormone transporters OATP1c1 and MCT8 during and after endotoxemia at the blood-brain barrier of male rodents.
abstract: There is increasing evidence that local thyroid hormone (TH) availability changes profoundly in inflammatory conditions due to altered expression of deiodinases that metabolize TH. It is largely unknown, however, how inflammation affects TH availability via the expression of TH transporters. In this study we examined the effect of bacterial lipopolysaccharide (LPS) administration on two TH transporters that are critically important for brain TH homeostasis, organic anion-transporting polypeptide 1c1 (OATP1c1), and monocarboxylate transporter 8 (MCT8). MRNA levels were studied by in situ hybridization and qPCR as well as protein levels by immunofluorescence in both the rat and mouse forebrain. The mRNA of both transporters decreased robustly in the first 9 hours after LPS injection, specifically in brain blood vessels; OATP1c1 mRNA in astrocytes and MCT8 mRNA in neurons remained unchanged. At 24 and/or 48 hours after LPS administration, OATP1c1 and MCT8 mRNAs increased markedly above control levels in brain vessels. OATP1c1 protein decreased markedly in vessels by 24 hours whereas MCT8 protein levels did not decrease significantly. These changes were highly similar in mice and rats. The data demonstrate that OATP1c1 and MCT8 expression are regulated in a parallel manner during inflammation at the blood-brain barrier of rodents. Given the indispensable role of both transporters in allowing TH access to the brain, the results suggest reduced brain TH uptake during systemic inflammation.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism (G.W., S.S.N., C.F., R.M.L.), Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; Department of Endocrine Neurobiology (J.S., P.M., B.G., C.F.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary; János Szentágothai PhD School of Neurosciences (P.M.), Semmelweis University, Budapest, 1085 Hungary; and Department of Neuroscience (R.M.L.), Tufts University School of Medicine, Boston, Massachusetts 02111.
authors.forename: Gábor
authors.initials: G
authors.lastname: Wittmann
authors.forename: Judit
authors.initials: J
authors.lastname: Szabon
authors.forename: Petra
authors.initials: P
authors.lastname: Mohácsik
authors.forename: Shira S
authors.initials: SS
authors.lastname: Nouriel
authors.forename: Balázs
authors.initials: B
authors.lastname: Gereben
authors.forename: Csaba
authors.initials: C
authors.lastname: Fekete
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lechan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D019446:Endotoxemia / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D027981:Symporters
chemical_list: D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; C464433:Oatp2 protein, mouse; D027701:Organic Cation Transport Proteins; C484257:Slc16a2 protein, mouse; C451262:Slco1c1 protein, rat; D027981:Symporters; C478998:monocarboxylate transporter 8, rat