Glutathione deficiency induced by cystine and/or methionine deprivation does not affect thyroid hormone deiodination in cultured rat hepatocytes and monkey hepatocarcinoma cells

Journal Article · Tue Sep 01 00:00:00 EDT 1981 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-109-3-844· OSTI ID:5369191

Sato, K; Robbins, J

To elucidate the recently advanced hypothesis that glutathione (L-gamma-glutamyl-L-cysteinyl glycine (GSH)) regulates deiodinating enzyme activities, accounting for the decreased conversion of T4 to T3 in the liver of fetal and starved animals, we investigated thyroid hormone metabolism in GSH-depleted neoplastic and normal hepatocytes. In monkey hepatocarcinoma cells, intracellular total GSH decreased below 10% of the control value (approximately 25 micrograms/mg protein) when cells were grown for 44 h in medium deficient in cystine and methionine or in cystine alone. The latter finding indicated that transsulfuration from methionine to cysteine was defective in these neoplastic cells. In primary cultured adult rat hepatocytes, on the other hand, the transsulfuration pathway was intact, and total GSH decreased below 10% of control (approximately 20 micrograms/mg protein) only in cells grown in cystine- and methionine-deficient medium. In both cell types, the oxidized GSH fraction remained constant (2-5% of total). Incubation with 125I-labeled T4 and T3, followed by chromatography, was used to evaluate 5-deiodination in hepatocarcinoma cells and both 5- and 5'-deiodination in normal hepatocytes. Deiodination was not decreased by GSH deficiency in either case, but was actually increased in hepatocarcinoma cells. This resulted from an increase in the Vmax of 5-deiodinase related to growth arrest. Diamide at 2 mM reversibly inhibited both 5'- and 5'-deiodination in rat hepatocytes, accompanied by decreased total GSH as well as increased GSH disulfide (27% of total). The data suggest that GSH is so abundant in the liver that hepatocytes can tolerate a greater than 90% decrease in intracellular concentration without any change in thyroid hormone deiodination and indicate that altered thyroid hormone metabolism in the fetus and in starvation cannot be accounted for by a decreased hepatic GSH concentration.

• OSTI ID: 5369191
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 109:3; ISSN ENDOA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550301 -- Cytology-- Tracer Techniques
551001 -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CARCINOMAS
CULTURE MEDIA
CYSTINE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DISULFIDES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
GLANDS
GLUTATHIONE
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIPOTROPIC FACTORS
LIVER
MAMMALS
METABOLISM
METHIONINE
MONKEYS
NEOPLASMS
NUCLEI
NUTRITIONAL DEFICIENCY
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
POLYPEPTIDES
PRIMATES
PROTEINS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
THYROID HORMONES
TRACER TECHNIQUES
TUMOR CELLS
VERTEBRATES