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 (Index) accumulate in serum of uremic patie nts and inhibit the active uptake of thyroxine (T-4) into hepatocytes. We tested the effects of CMPF and Index on the uptake of [I-125] trii odothyronine (T-3) and [I-125]T-4 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. Experim ents were performed at 37 degrees C in the same medium with 0.5% bovin e serum albumin (BSA; [I-125]T-3 uptake and TSH secretion) or 0.1% BSA ([I-125]T-4 uptake). The 15-min uptake of [I-125]T-3 amounted to 0.07 4 +/- 0.003 fmol/pM free T-3 (n = 23) and that of [I-125]T-4 to 0.033 +/- 0.002 fmolipM free T-4 (n = 32). Preincubation (30 min) and incuba tion (15 min) with CMPF (20-200 mu M) did not alter the uptake of [I-1 25]T-3 but reduced [I-125]T-4 uptake by 27% (P < 0.05) at the highest concentration tested. Index (40-400 mu M) did not affect the uptake of [I-125]T-3 or [I-125]T-4 CMPF (40 mu M) and Index (80 mu M) did not d irectly affect the basal or thyrotropin-releasing hormone (TRH)-induce d TSH release nor interfere with the effect of 10 nM T-3 on TRH-induce d TSH release. In conclusion, the absence of inhibitory effects of CMP F or Index 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 c arriers for the intracellular availability of T-3.