Effects of 5,5'-diphenylhydantoin on thyroxine and 3,5,3'-triiodothyronine concentrations in several tissues of the rat

Journal Article · Mon Jan 01 00:00:00 EST 1990 · Endocrinology; (USA)

DOI:https://doi.org/10.1210/endo-126-1-186· OSTI ID:7168206

Schroeder-van der Elst, J Pv; van der Heide, D ^[1]

---

1. University Hospital, Leiden (Netherlands)

We studied the effect of 5,5'-diphenylhydantoin (phenytoin, DPH) on the metabolism of thyroid hormones, the intracellular concentration of T4, and the source and concentration of T3. Two groups of six male Wistar rats received a continuous infusion of 10 ml saline/rat. day. One group received DPH in their food (50 mg/kg BW) for 20 days. For both groups (125I)T4 and (131I)T3 were added to the infusion fluid for the last 10 and 7 days, respectively. At isotopic equilibrium the rats were bled and perfused. Compared to the controls, plasma T4 and T3 in the DPH group were reduced (22% and 31%, respectively); TSH did not change. The rate of production of T4 and the plasma appearance rate for T3 were decreased. Thyroidal T3 production was markedly reduced. From the increased (125I)T3/(125I)T4 ratio for plasma, it follows that total body conversion was enhanced. The tissue T4 concentrations decreased in parallel with the plasma T4 level. Total T3 was reduced in all organs. In tissues in which local conversion does not occur, i.e. heart and muscle, the decrease reflected the decrease in plasma T3. In the liver both plasma-derived T3 and locally produced T3 were diminished. In cerebellum and brain the plasma-derived T3 pool was even smaller than was expected from the decrease in plasma T3. This was partly compensated by an increase in local conversion. Only for these two organs was the decrease in the tissue/plasma ratio for (131I)T3 significant. Our results suggest tissue hypothyroidism, caused by a decrease in the production of T4 and T3, which is partly compensated by increased conversion in several organs. The transport of T3 into cerebellum and brain is disturbed, which can be attributed to the mode of action of DPH.

• OSTI ID: 7168206
• Journal Information: Endocrinology; (USA), Vol. 126:1; ISSN 0013-7227
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTICONVULSANTS
BIOCHEMICAL REACTION KINETICS
HYPOTHYROIDISM
PATHOGENESIS
THYROXINE
METABOLISM
TRIIODOTHYRONINE
IODINE 125
IODINE 131
RATS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE DISEASES
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
PEPTIDE HORMONES
RADIOISOTOPES
REACTION KINETICS
RODENTS
THYROID HORMONES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
550501 - Metabolism- Tracer Techniques
550901 - Pathology- Tracer Techniques