Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, AMINO-ACID TRANSPORTER, BLOOD-BRAIN-BARRIER, ORGANIC ANION TRANSPORTER, HERNDON-DUDLEY-SYNDROME, MONOCARBOXYLATE TRANSPORTER-8, FUNCTIONAL-CHARACTERIZATION, EXPRESSION CLONING, HEAVY-CHAIN, MCT8, IDENTIFICATION, Amino Acid Transport Systems, Neutral, Animals, COS Cells, Cell Line, Tumor, Cell Membrane, Chickens, Embryo, Nonmammalian, Humans, Immunohistochemistry, In Situ Hybridization, Large Neutral Amino Acid-Transporter 1, Monocarboxylic Acid Transporters, Organic Anion Transporters, Thyroid Hormones, 06 Biological Sciences, 07 Agricultural and Veterinary Sciences, 11 Medical and Health Sciences, 3202 Clinical sciences

Abstract:

Thyroid hormone (TH) transmembrane transporters are key regulators of TH availability in target cells where correct TH signaling is essential for normal development. Although the chicken embryo is a valuable model for developmental studies, the only functionally characterized chicken TH transporter so far is the organic anion transporting polypeptide 1C1 (OATP1C1). We therefore cloned the chicken L-type amino acid transporter 1 (LAT1) and the monocarboxylate transporters 8 (MCT8) and 10 (MCT10), and functionally characterized them, together with OATP1C1, in JEG3, COS1, and DF-1 cells. In addition, we used in situ hybridization to study their mRNA expression pattern during development. MCT8 and OATP1C1 are both high affinity transporters for the prohormone T4, whereas receptor-active T3 is preferably transported by MCT8 and MCT10. The latter one shows lower affinity but has a high Vmax and seems to be especially good at T3 export. Also, LAT1 has a lower affinity for its preferred substrate 3,3'-diiodothyronine. Reverse T3 is transported by all 4 TH transporters and is a good export product for OATP1C1. TH transporters are strongly expressed in eye (LAT1, MCT8, MCT10), pancreas (LAT1, MCT10), kidney, and testis (MCT8). Their extensive expression in the central nervous system, especially at the brain barriers, indicates an important role in brain development. In conclusion, we show TH transport by chicken MCT8, MCT10, and LAT1. Together with OATP1C1, these transporters have functional characteristics similar to their mammalian orthologs and are interesting target genes to further elucidate the role of THs during embryonic development.