ABSTRACT
We have elucidated the action of tri-iodothyronine (T3) on the synthesis and secretion of seven major plasma proteins in a human hepatoblastoma 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 treated with various concentrations of T3. During the first 24 h of T3 treatment, accumulation of α-fetoprotein in the medium was decreased in a dose-dependent manner (10−11-10−8 m), and the inhibitory effect was enhanced during the second 24 h of T3 treatment. On the other hand, α1-antitrypsin accumulation in the medium during the second 24 h of hormone treatment was decreased by T3 (10−9–10−8 m), although no change in accumulation was observed during the first 24 h of T3 treatment.
The newly synthesized [35S]Met-labelled α1-acid glycoprotein was increased by T3 and reached 3·4-fold within 37 h of 10−8 m T3 treatment. The stimulatory effect increased time-dependently (4·6fold after 61 h). In contrast, the synthesis of α-fetoprotein was reduced to half of that of the control after T3 treatment for 37 h.
Although the content of newly synthesized [35S]α1-antitrypsin was not affected by 10−8m T3 treatment during 3 days of hormone treatment, the accumulation of α1-antitrypsin in the medium decreased to 87%; in contrast, total cellular newly synthesized α1-antitrypsin increased to 105–130% of that of the control. From these results, it is suggested that α1-antitrypsin secretion might be suppressed by T3 treatment. However, T3 did not affect the accumulation of albumin, transferrin, fibronectin and α2-macroglobulin in the medium throughout the experiments.
It was shown that T3 has diverse control mechanisms on the synthesis and secretion of plasma proteins in Hep G2 cells: stimulation (α1-acid glycoprotein) or inhibition (α-fetoprotein) of plasma protein synthesis, and inhibition of protein secretion (α1-antitrypsin).
Sulphation of proteins secreted by a human hepatoma-derived cell line. Sulphation of N-linked oligosaccharides on α2HS-glycoprotein