Effects of dexamethasone on kinetics and distribution of triiodothyronine in the rat
Studies were designed to examine the effects of the glucocorticoid dexamethasone (Dex) on the distribution and turnover of T3 separately from its effects on the pituitary and thyroid. Male Sprague-Dawley rats (200-250 g) were surgically thyroidectomized and given a replacement dose of T4 (1.6 micrograms/day X 100 g BW) throughout the experiment via a sc implanted osmotic minipump. Six or 7 days after starting the T4 infusion, each animal was given (/sup 125/I)T3 by constant infusion (via a second minipump) for 5 or 6 days and, during the final 5 days, either Dex (0.15 mg/day X 100 g) or saline in a third minipump. Methanol extracts of serum and tissues removed at the end of the infusion were analyzed for (/sup 125/I)T3 concentration by high performance liquid chromatography. The MCR, computed from the infusion rate of tracer and the serum concentration of (/sup 125/I)T3 at the end of the infusion, averaged 25.7 +/- 1.3 (+/-SE) ml/h X 100 g in the controls and 15.1 +/- 2.6 in the Dex-treated rats. Serum T3 (RIA) concentrations were similar in the two groups. The plasma T3 production rate was decreased from 9.51 +/- 1.14 ng/h X 100 g in controls to 5.13 +/- 1.16 in the Dex-treated animals. The fraction of administered T4 converted to T3 was reduced from 0.21 to 0.11 by Dex treatment. Tissue to serum (T/S) (/sup 125/I)T3 concentration ratios were significantly decreased by Dex to approximately 50% of the control value in each of the tissues sampled (liver, kidney, and skeletal muscle). The rate of T4 5'-deiodination in vitro was diminished in homogenates of livers from Dex-treated animals when the incubation was performed with and without added thiol as cofactor, indicating that the hepatic level of active T4 5'-deiodinase is reduced by Dex. Thus, Dex causes multiple alterations in T3 metabolism. Total body T3 production from T4 in extrathyroid sites, and in the liver in particular, is reduced.
- Research Organization:
- Veterans Administration Medical Center, San Francisco, CA
- OSTI ID:
- 7013795
- Journal Information:
- Endocrinology; (United States), Vol. 114:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DEXAMETHASONE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
THYROXINE
TISSUE DISTRIBUTION
TRIIODOTHYRONINE
METABOLISM
CLEARANCE
GLUCOCORTICOIDS
IODINE
IODINE 125
MALES
RATS
TRACER TECHNIQUES
ADRENAL HORMONES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CORTICOSTEROIDS
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
HALOGENS
HORMONES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KETONES
KINETICS
MAMMALS
NONMETALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
PEPTIDE HORMONES
PREGNANES
RADIOISOTOPES
REACTION KINETICS
RODENTS
STEROID HORMONES
STEROIDS
THYROID HORMONES
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques