Effects of a furan fatty acid and indoxyl sulfate on thyroid hormone uptake in cultured anterior pituitary cells.
A furan fatty acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and indoxyl sulfate (Indox) accumulate in serum of uremic patients and inhibit the active uptake of thyroxine (T4) into hepatocytes. We tested the effects of CMPF and Indox on the uptake of [125I]triiodothyronine (T3) and [125I]T4 and thyroid-stimulating hormone (TSH) release in anterior pituitary cells. Pituitary cells (500,000/well) were cultured for 3 days in medium with 10% fetal calf serum. Experiments were performed at 37 degrees C in the same medium with 0.5% bovine serum albumin (BSA; [125I]T3 uptake and TSH secretion) or 0.1% BSA ([125I]T4 uptake). The 15-min uptake of [125I]T3 amounted to 0.074 +/- 0.003 fmol/pM free T3 (n = 23) and that of [125I]T4 to 0.033 +/- 0.002 fmol/pM free T4 (n = 32). Preincubation (30 min) and incubation (15 min) with CMPF (20-200 microM) did not alter the uptake of [125I]T3 but reduced [125I]T4 uptake by 27% (P < 0.05) at the highest concentration tested. Indox (40-400 microM) did not affect the uptake of [125I]T3 or [125I]T4. CMPF (40 microM) and Indox (80 microM) did not directly affect the basal or thyrotropin-releasing hormone (TRH)-induced TSH release nor interfere with the effect of 10 nM T3 on TRH-induced TSH release. In conclusion, the absence of inhibitory effects of CMPF or Indox on thyroid hormone uptake by pituitary cells suggests that the transport mechanism is regulated differently compared with that in hepatocytes and underscores the significance of the thyroid hormone carriers for the intracellular availability of T3.
Everts
M E
ME
Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
Lim
C F
CF
Moerings
E P
EP
Docter
R
R
Visser
T J
TJ
De Jong
M
M
Krenning
E P
EP
Hennemann
G
G
D000818:Animals; D002478:Cells, Cultured; D005663:Furans / Q000494:pharmacology*; D007200:Indican / Q000494:pharmacology*; D008297:Male; D009994:Osmolar Concentration; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D013974:Thyroxine / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000493:pharmacokinetics* / Q000494:pharmacology
D005663:Furans; D011422:Propionates; D014284:Triiodothyronine; C041693:3-carboxy-4-methyl-5-propyl-2-furanpropionic acid; D013972:Thyrotropin; D007200:Indican; D013974:Thyroxine