ACTIONS OF 3,5,3'-TRI-IODOTHYRONINE ON THE SYNTHESIS AND SECRETION OFMAJOR PLASMA-PROTEINS BY A HUMAN HEPATOBLASTOMA CELL-LINE (HEP G2)

We have elucidated the action of tri-iodothyronine (T-3) on the synthe sis and secretion of seven major plasma proteins in a human hepatoblas toma cell line, Hep G2, and established an in vitro experimental model of human liver cells for the study of the mechanism of the action of thyroid hormone. Hep G2 cells cultured in serum-free medium were treat ed with various concentrations of T-3. During the first 24 h of T-3 tr eatment, accumulation of alpha-fetoprotein in the medium was decreased in a dose-dependent manner (10(-11)-10(-8) M), and the inhibitory eff ect was enhanced during the second 24 h of T-3 treatment. On the other hand, alpha(1)-antitrypsin accumulation in the medium during the seco nd 24 h of hormone treatment was decreased by T-3 (10(-9)-10(-8) M), a lthough no change in accumulation was observed during the first 24 h o f T-3 treatment. The newly synthesized [S-35]Met-labelled alpha(1)-aci d glycoprotein was increased by T-3 and reached 3.4-fold within 37 h o f 10(-8) M T-3 treatment. The stimulatory effect increased time-depend ently (4.6-fold after 61 h). In contrast, the synthesis of alpha-fetop rotein was reduced to half of that of the control after T-3 treatment for 37 h. Although the content of newly synthesized [S-35]alpha(1)-ant itrypsin was not affected by 10(-8) M T-3 treatment during 3 days of h ormone treatment, the accumulation of alpha(1)-antitrypsin in the medi um decreased to 87%; in contrast, total cellular newly synthesized alp ha(1)-antitrypsin increased to 105-130% of that of the control. From t hese results, it is suggested that alpha(1)-antitrypsin secretion migh t be suppressed by T-3 treatment. However, T-3 did not affect the accu mulation of albumin, transferrin, fibronectin and alpha(2)-macroglobul in in the medium throughout the experiments. It was shown that T-3 has diverse control mechanisms on the synthesis and secretion of plasma p roteins in Hep G2 cells: stimulation (alpha(1)-acid glycoprotein) or i nhibition (alpha-fetoprotein) of plasma protein synthesis, and inhibit ion of protein secretion (alpha(1)-antitrypsin).