Thyroxine-binding globulin biosynthesis in isolated monkey hepatocytes

Abstract

Thyroxine-binding globulin biosynthesis was demonstrated in hepatocytes isolated from normal adult Rhesus monkeys. Dispersed cells were obtained by in situ liver perfusion with collagenase, hyaluronidase and EDTA. Conditions for optimum cell survival and incorporation of radioactive leucine into newly synthesized proteins were defined. Protein synthesis, and specifically thyroxine-binding globulin synthesis, were shown to continue throughout the incubation period, while cell survival remained high (75% excluded trypan blue after 6h). Incubation medium, cytosol and a particulate fraction (extracted with digitonin) were analyzed for thyroxine-binding globulin. After extensive dialysis and purification by affinity chromatography, newly synthesized thyroxine-binding globulin was identified by specific double-antibody immunoprecipitation and by immunodiffusion and immunoelectrophoresis with autoradiography. Newly synthesized thyroxine-binding globulin was present after 4 h of incubation. After 6 h, the total synthesized had increased to 150% of the 4 h value, while the fraction present in the medium and increased to 300%, indicating probable thyroxine-binding globulin secretion

Increased serum reverse triiodothyronine levels at diagnosis of hepatocellular carcinoma in patients with compensated HCV‐related liver cirrhosis

“…However, patients with uncomplicated cirrhosis have also been shown to have elevated serum TBG levels higher than those previously reported by others (Alexopoulos et al ., 1988; Nagasue et al ., 1997). Indeed, TBG is physiologically produced by the liver cells (Glinoer et al ., 1976), and the inflammatory process and hepatocyte regeneration could be important stimulatory factors for the synthesis of this protein in patients with active cirrhosis (Ross et al ., 1983; Huang & Liaw, 1990). However, different mechanisms have been proposed for the increase in TBG levels in the patients with cirrhosis and in those with HCC (Ross et al ., 1983; Bartalena et al ., 1984; Huang & Liaw, 1990); these are not confirmed in our study.…”

“…Most circulating T3, the biologically active thyroid hormone, is produced in the liver by type I deiodinase, which induces the 5′ deiodination of T4 (Visser et al ., 1988; Stralen et al ., 1996; Germain & Galton, 1997). Moreover, the liver is the site of synthesis of the thyroid hormone‐binding proteins (Glinoer et al ., 1976; Robbins et al ., 1978). Changes in the serum levels of thyroid hormones and their binding proteins have been described in patients with cirrhosis (Chopra et al ., 1974; Nomura et al ., 1975; Schussler et al ., 1978; Kabadi & Premachandra, 1983; D’Azzo et al ., 1985; Shimada et al ., 1988), as well as in those with HCC (Gershengorn et al ., 1976; Kalk et al ., 1982; Terui et al ., 1987; Alexopoulos et al ., 1988; Shimada et al ., 1988; Huang & Liaw, 1990; Nagasue et al ., 1997).…”

Circulating Thyroid Hormones in Primates with Mild or Severe Hepatitis Following Liver Transplantation

“…We have no ready explanation as to why this apparent rise in TBG in the anicteric animals was so transient. TBG is produced by the liver (Glinoer, Gershengorn and Robbins 1976). It is likely that the rise in TBG levels reflected an increase in synthesis and secretion, rather than simple leakage from damaged hepatocytes -there was no rise in TBG in those animals with evidence of more severe liver damage.…”

Thyroxine-binding globulin synthesis by hepatocarcinoma cells in continuous culture: Effect of physiological concentrations of thyroxine

“…TBG was identified in the média by immunochemical and T4-binding techniques. The anti-TBG sérum used in thèse studies was characterized previously (1). Newly synthesized TBG was identified by immunoelectrophoresis followed by autoradiography (1).…”

“…The anti-TBG sérum used in thèse studies was characterized previously (1). Newly synthesized TBG was identified by immunoelectrophoresis followed by autoradiography (1). T^-binding by TBG in the média was shown after addition of trace amounts of [•'•^^IlT^ (Abbott Laboratories, Chicago, IL) followed by immunoprecipitation (1) and compared to binding by standard TBG.…”