Comparison of mechanisms mediating uptake and efflux of thyroid hormones in the human choriocarcinoma cell line, JAR

We compared the specificities of transport mechanisms for uptake and efflux of thyroid hormones in cells of the human choriocarcinoma cell line, JAR, to determine whether triiodothyronine (T-3), thyroxine (T-4) and reverse T-3 (rT(3)) are carried by the same transport mechanism. Uptake of I-125-T-3, I-125-T-4 and I-125-rT(3) was saturable and stereospecific, but not specific for T-3, T-4 and rT(3), as unlabelled L-stereoisomers of the thyroid hormones inhibited uptake of each of the radiolabelled hormones. Efflux of I-125-T-3 was also saturable and stereospecific and was inhibited by T-4 and rT(3). Efflux of I-125-T-4 or I-125-rT(3) was, in contrast, not significantly inhibited by any of the unlabelled thyroid hormones tested. A range of compounds known to interfere with receptor-mediated thyroid hormone uptake in cells inhibited uptake of I-125-T-3 and I-125-rT(3), but not I-125-T-4. We conclude that in JAR cells uptake and efflux of I-125-T-3 are mediated by saturable and stereospecific membrane transport processes. In contrast, the uptake, but not the efflux, of I-125-T-4 and I-125-rT(3) is saturable and stereospecific, indicating that uptake and efflux of T-4 and rT(3) in JAR cells occur by different mechanisms. These results suggest that in JAR cells thyroid hormones may be transported by at least two types of transporters: a low affinity iodothyronine transporter (Michaelis constant, K-m, around 1 mu M) which interacts with T-3, T-4 and rT(3), but not amino acids, and an amino acid transporter which takes up T-3, but not T-4 or rT(3). Efflux of T-4 and rT(3) appears to occur by passive diffusion in these cells