Reexamination of the proposed inactivation of thyroid peroxidase in the rat thyroid by propylthiouracil
The antithyroid drug 6-propylthiouracil (PTU) was previously shown in our laboratory to have an unexpectedly prolonged inhibitory effect on iodination in the thyroid glands of rats. Eighteen hours after injection of a relatively small dose, iodination in the thyroid remained inhibited by more than 90%. We previously suggested that the prolonged inhibitory effect might be due to inactivation of thyroid peroxidase (TPO), a reaction previously shown to occur under certain conditions in an in vitro iodinating system containing highly purified TPO. However, the analytical procedure used in our earlier study did not exclude the possibility that sufficient PTU remained in the thyroid even after 18 h to inhibit TPO-catalyzed iodination by a reversible mechanism. Development of an improved analytical procedure, based on HPLC, led us to reexamine the mechanism of the prolonged inhibitory effect of PTU on iodination in rat thyroid glands. Rats were injected with (35S)PTU (1 mumol/100 g BW), and ultrafiltrates prepared from their homogenized thyroid glands were analyzed by HPLC. The major 35S-labeled metabolites were identified as sulfate/sulfite, PTU sulfinate, and PTU sulfonate. However, even after 18 h, a significant amount of unchanged (35S)PTU was also present. The calculated mean concentration of residual PTU was 20 microM, a sufficiently high level to explain the observed inhibition of iodination on the basis of a reversible mechanism. Experiments were also performed to examine the intrathyroidal distribution of 35S at intervals after the injection of (35S)PTU. All of the oxidation products of PTU showed marked increases between 2 and 16 h after injection. Based on our view that TPO is the major mediator of intrathyroidal metabolism of PTU, this observation is inconsistent with our previous proposal that TPO is inactivated after PTU injection.
- Research Organization:
- Univ. of Texas Southwestern Medical Center, Dallas (USA)
- OSTI ID:
- 5934829
- Journal Information:
- Endocrinology; (United States), Vol. 124:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
PEROXIDASES
ENZYME ACTIVITY
THIOURACIL
BIOCHEMICAL REACTION KINETICS
THYROID
IODINATION
INHIBITION
IODIDES
ISOTOPE DILUTION
METABOLITES
RATS
SULFUR 35
ANIMALS
ANTIMETABOLITES
ANTITHYROID DRUGS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DRUGS
ENDOCRINE GLANDS
ENZYMES
EVEN-ODD NUCLEI
GLANDS
HALIDES
HALOGEN COMPOUNDS
HALOGENATION
HETEROCYCLIC COMPOUNDS
HORMONE ANTAGONISTS
HYDROXY COMPOUNDS
IODINE COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDOREDUCTASES
PYRIMIDINES
RADIOISOTOPES
REACTION KINETICS
RODENTS
SULFUR ISOTOPES
THIOLS
TRACER TECHNIQUES
URACILS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques