Effect of hypothyroidism on pathways for iodothyronine and tryptophan uptake into rat adipocytes.
Adipocytes are an important target tissue for thyroid hormone action, but little is known of the mechanisms of thyroid hormone entry into the cells. The present results show a strong interaction between transport of iodothyronines [L-thyroxine (T4), L-triiodothyronine (T3), reverse T3 (rT3)], aromatic amino acids, and the System L amino acid transport inhibitor 2-amino[2,2,1]heptane-2-carboxylic acid (BCH) in white adipocytes. System L appears to be a major pathway of iodothyronine and large neutral amino acid entry into these cells in the euthyroid state. We also demonstrate expression of the CD98hc peptide subunit of the System L transporter in adipocyte cell membranes. Experimental hypothyroidism (28-day propylthiouracil treatment) has no significant effect on System L-like transport of the amino acid tryptophan in adipocytes. In contrast, uptake of T3 and especially T4 is substantially reduced in adipocytes from hypothyroid rats, partly due to reduction of the BCH-sensitive transport component. Transport of iodothyronines and amino acids in adipocytes therefore becomes decoupled in the hypothyroid state, as occurs similarly in liver cells. This may be due to downregulation or dissociation of iodothyronine receptors from the System L transporter complex. Regulation of iodothyronine turnover in fat cells by this type of mechanism could contribute significantly to modulation of T4-T3/rT3 metabolism in the hypothyroid state.
Ritchie
J W
JW
School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
Collingwood
C J
CJ
Taylor
P M
PM
D017667:Adipocytes / Q000378:metabolism*; D000598:Amino Acids, Cyclic / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D027261:Fusion Regulatory Protein-1; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013974:Thyroxine / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000493:pharmacokinetics*; D014285:Triiodothyronine, Reverse / Q000493:pharmacokinetics*; D014364:Tryptophan / Q000493:pharmacokinetics*
D000598:Amino Acids, Cyclic; D015703:Antigens, CD; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; D014284:Triiodothyronine; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D014285:Triiodothyronine, Reverse; D014364:Tryptophan; D013974:Thyroxine; D003891:Desipramine