Metabolism of 3,3'-diiodothyronine in rat hepatocytes: interaction of sulfation with deiodination
Production of 3,3'-diiodothyronine (3,3'-T2) is an important step in the peripheral metabolism of thyroid hormone in man. The rapid clearance of 3,3'-T2 is accomplished to a large extent in the liver. The mechanisms of this process have been studied in detail using monolayers of freshly isolated rat hepatocytes. After incubation with 3,(3'-/sup 125/I)T2, chromatographic analysis of the medium revealed two major metabolic routes: outer ring deiodination and sulfation. The authors recently demonstrated that sulfate conjugation precedes and in effect accelerates deiodination of 3,3'-T2. In media containing different serum concentrations the cellular clearance rate was determined by the nonprotein-bound fraction of 3,3'-T2. At substrate concentrations below 10(-8) M /sup 125/I- was the main product observed. At higher concentrations deiodination became saturated, and 3,3'-T2 sulfate (T2S) accumulated in the medium. Saturation of 3,3'-T2 clearance was found to occur only at very high (greater than 10(-6)M) substrate concentrations. The sulfating capacity of the cells exceeded that of deiodination by at least 20-fold. Deiodination was completely inhibited by 10(-4) M propylthiouracil or thiouracil, resulting in the accumulation of T2S while clearance of 3,3'-T2 was little affected. Hepatocytes from 72-h fasted rats showed a significant reduction of deiodination but unimpaired sulfation. Other iodothyronines interfered with 3,3'-T2 metabolism. Deiodination was strongly inhibited by 2 microM T4 and rT3 (80%) but little by T3 (15%), whereas the clearance of 3,3'-T2 was reduced by 27% (T4 and rT3) and 12% (T3). It is concluded that the rapid hepatic clearance of 3,3'-T2 is determined by the sulfate-transferring capacity of the liver cells. Subsequent outer ring deiodination of the intermediate T2S is inhibited by propylthiouracil and by fasting, essentially without an effect on overall 3,3'-T2 clearance.
- Research Organization:
- Erasmus Univ. Medical School, Rotterdam, Netherland
- OSTI ID:
- 6204523
- Journal Information:
- Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 115:3; ISSN ENDOA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
ANTITHYROID DRUGS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DEHALOGENATION
DEIODINATION
DIGESTIVE SYSTEM
DIIODOTHYRONINE
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
FASTING
GLANDS
HORMONE ANTAGONISTS
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
LIVER
MAMMALS
METABOLISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PEPTIDE HORMONES
RADIOISOTOPES
RATS
REACTION KINETICS
RESPONSE MODIFYING FACTORS
RODENTS
SEPARATION PROCESSES
SULFATES
SULFUR COMPOUNDS
THYROID HORMONES
THYROXINE
TRIIODOTHYRONINE
VERTEBRATES