Different transporters for tri-iodothyronine (T3) and thyroxine (T4) in the human choriocarcinoma cell line, JAR

Abstract

We investigated transport systems for tri-iodothyronine (T3) and thyroxine (T4) in the human choriocarcinoma cell line, JAR, using a range of structurally similar compounds to determine whether these thyroid hormones are transported by common or different mechanisms. Saturable T3 but not saturable T4 uptake was inhibited by a wide range of aromatic compounds (nitrendipine, nifedipine, verapamil, meclofenamic acid, mefenamic acid, diazepam, phenytoin). Nitrendipine and diazepam were the most effective inhibitors of saturable thyroid hormone uptake. Nitrendipine decreased the Km for T4 uptake from a control value of around 500 nM to around 300 nM (n = 6). In contrast, the Km for T3 uptake was increased from a control value of around 300 nM to around 750 nM (n=4). Diazepam had similar effects. This divergent shift in affinity for the uptake of T3 and T4 suggested that separate uptake systems exist for these two thyroid hormones. This provides evidence for at least two transporters mediating uptake of T3 and T4 in JAR cells: a specific T4 transporter that does not interact with T3 or structurally similar compounds; and a shared iodothyronine transporter that interacts with T3, T4, nitrendipine and diazepam.