Modulation of nuclear T3 binding by T3 in a human hepatocyte cell-line (Chang-liver) - T3 stimulation of cell growth but not of malic enzyme, glucose-6-phosphatdehydrogenase or 6-phosphogluconate-dehydrogenase.
The T3 modulation of nuclear T3 binding (NBT3), the T3 effect on cell growth, and the T3 and insulin effects on malic enzyme (ME), glucose-6-phosphat-dehydrogenase (G6PD) and 6-phosphogluconat-dehydrogenase (G6PD) were studied in a human hepatocyte cell-line (Chang-liver). T3 was bound to a high affinity site with (mean +/- SD, n = 7) Ka1 3.0 +/- 0.3 * 10(9) M-1 and maximal binding capacity (MBC1 112.1 +/- 20.7 fmol/mg DNA, and to a low affinity site with (median, (range), n = 7) Ka2 1.4 (0.6 - 2.6) * 10(7) M-1 and MBC2 766 (461-2687) fmol/mg DNA. Incubation of cells with T3 6 nmol/l for 20 hours reduced the area under the T3 binding curves (AUC) to 80.9% +/- 10.0% of AUC in cells incubated without T3 (p < 0.01, n = 7). The downregulation, being reversible and associated with receptor saturation, was caused by a reduction in MBC1 of the high affinity site to 66.6 fmol/mg DNA, whereas Ka1 was unchanged. T3 stimulated cell growth (p < 0.05, n = 8), but had no effect on the activities of ME, G6PD, and 6PGD. Insulin (1 mumol/l) enhanced the activities of ME (p < 0.01, n = 6) and 6PGD (p < 0.05, n = 6).


CONCLUSIONS
The cellular effects of T3 in the human hepatocyte cell-line was: 1) a reversible modulation of NBT3 associated to receptor saturation; 2) stimulation of cell growth; 3) contrary to the findings in rat hepatocytes no stimulation of ME, G6PD or 6PGD. Insulin enhanced ME and 6PGD.
Matzen
L E
LE
Department of Clinical Chemistry, Odense University Hospital, Denmark.
Kristensen
S R
SR
Kvetny
J
J
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism*; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
D007328:Insulin; D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D004247:DNA; D008291:Malate Dehydrogenase; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D013974:Thyroxine