Thyroid hormone transport by the rat fatty acid translocase.
We examined the hypothesis that rat fatty acid translocase (rFAT) mediates the cellular uptake of T(3) and other iodothyronines. Uninjected Xenopus laevis oocytes and oocytes injected 4 d previously with rFAT cRNA were incubated for 60 min at 25 C in medium containing 0.01-10 micro M [(125)I]T(3) and 0.1% BSA, or 1-100 micro M [(3)H]oleic acid and 0.5% BSA. Injection of rFAT cRNA resulted in a 1.9-fold increase in uptake of T(3) (10 nM) and a 1.4-fold increase in uptake of oleic acid (100 micro M). Total T(3) uptake was lower in the presence than in the absence of BSA, but relative to the free T(3) concentration, uptake was increased by BSA. The fold induction of T(3) uptake by rFAT was not influenced by BSA. By analyzing uptake as a function of the ligand concentration, we estimated a K(m) value of 3.6 micro M for (total) T(3) and 56 micro M for (total) oleic acid. In addition to T(3), rFAT mediates the uptake of T(4), rT(3), 3,3'-diiodothyronine, and T(3) sulfate. The injection of human type III deiodinase cRNA with or without rFAT cRNA resulted in the complete deiodination of T(3) taken up by the oocytes, indicating that T(3) is indeed transported to the cytoplasm. In conclusion, our results demonstrate transport of T(3) and other iodothyronines by rFAT.
van der Putten
Haidy H A G M
HH
Department of Veterinary Anatomy and Physiology, Utrecht University, 3508 TD Utrecht, The Netherlands.
Friesema
Edith C H
EC
Abumrad
Nada A
NA
Everts
Maria E
ME
Visser
Theo J
TJ
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D018955:CD36 Antigens; D018076:DNA, Complementary / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D019301:Oleic Acid / Q000493:pharmacokinetics; D009865:Oocytes / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014284:Triiodothyronine / Q000493:pharmacokinetics*; D014316:Tritium; D014982:Xenopus laevis
D018955:CD36 Antigens; D018076:DNA, Complementary; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D027361:Organic Anion Transporters; D014284:Triiodothyronine; D014316:Tritium; D019301:Oleic Acid