The effect of short term feeding of the antioxidant triethyleneglycol-bis-3(3-tert-butyl-4-hydroxy-5-methyl)propionate on serum thyrotropin and thyroid hormones in the male rat.
Male rats were fed triethyleneglycol-bis-3(3-tert-butyl-4-hydroxy-5-methyl)propionate (TK 12627) admixed with the food at a concentration of 1000 ppm for 3, 6, 13, and 20 days. Treatment resulted in time-dependent and marked increases in serum levels of thyrotropin (TSH) and reverse triiodothyronine (rT3). Serum levels of thyroxine (T4) were slightly and transiently decreased, whereas triiodothyronine (T3) levels decreased by 35-50% at all time periods. Treatment with 50, 150, 500, and 1000 ppm for 2 weeks resulted in dose-related increases in thyroid and liver weights, follicular hypertrophy of the thyroid, morphological changes of the pituitaries, liver hypertrophy, and similar changes in the serum parameters described above. At 50 ppm, no alterations in the weights and morphology of the liver, thyroid, or pituitary nor in the serum levels of TSH or T4 were observed. The effects of TK 12627 observed at a dose of 1000 ppm for 2 weeks were reversible after cessation of treatment. Decreases in T3, increases in rT3, and no change in T4 serum levels were also obtained when thyroidectomized T4-substituted rats were treated with 1000 ppm TK 12627 for 28 days, indicating that the effects of TK 12627 are probably due to inhibition of the 5' monodeiodination of T4 to T3 and rT3 to diiodothyronine with compensatory increases in thyroid hormone conjugation at extrathyroidal sites.
Muakkassah-Kelly
S F
SF
Central Toxicology Unit, CIBA-GEIGY, Ltd., Basel, Switzerland.
Krinke
A L
AL
Malinowski
W
W
Stäubli
W
W
Bentley
P
P
Waechter
F
F
Juge-Aubry
C
C
Burger
A G
AG
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D006984:Hypertrophy; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood*; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood*; D013997:Time Factors
D000975:Antioxidants; D013963:Thyroid Hormones; C066840:TK 12627; D011092:Polyethylene Glycols; D013972:Thyrotropin