Influence of 3,5-dimethyl-3'-isopropyl-L-thyronine on thyroid state and gestational outcome in the Wistar rat.
3,5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT, CAS 26384-44-1), a non-halogenated, artificial analogue of the thyroid hormone T3, was administered once daily by intragastric gavage to pregnant Wistar rats on days 17-20 of gestation to elucidate the effects of DIMIT on maternal and foetal thyroid state and gestational outcome under the influence of low iodine or iodine excess nutrition. Doses of 20 micrograms.kg-1.d-1 and 150 micrograms.kg-1.d-1 DIMIT were applied. Throughout pregnancy the animals were kept on low iodine diet and either on iodine free drinking water or iodine excess. There was no statistically significant effect on maternal body weight, weight of living foetus, the rate of intra-uterine death before day 16 of gestation, water and food consumption, and no hint of maternal thyrotoxicosis. The vital off-spring did not reveal any signs of gross malformation. DIMIT decreased serum TSH both in dams and foetus, and diminished the TSH stock of the pituitary gland of the dams. T3-levels were also lowered in maternal serum by DIMIT. These DIMIT induced effects were observed irrespective of iodine deficiency or excess. There was no difference in foetal mortality before onset of DIMIT-treatment, but the gestational death rate increased in a dose-related manner by the administration of DIMIT. This serious adverse effect became apparent at a DIMIT-dose that is not sufficient for a complete compensation of foetal hypothyroidism in utero. The higher prenatal mortality was accompanied by a decreased placental weight, but not by a reduced body weight of surviving foetus.
Jekat
F W
FW
Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität Münster, Fed. Rep. of Germany.
Sourgens
H
H
Kemper
F H
FH
D000818:Animals; D005260:Female; D005313:Fetal Death; D007455:Iodine / Q000172:deficiency / Q000633:toxicity; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D051381:Rats; D017208:Rats, Wistar; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000187:drug effects*; D013970:Thyronines / Q000494:pharmacology*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism
D013970:Thyronines; D014284:Triiodothyronine; C022861:3,5-dimethyl-3'-isopropyl-L-thyronine; D013972:Thyrotropin; D007455:Iodine