Paradoxical effect of perchlorate on thyroidal weight, glucose 6-phosphate dehydrogenase and polyamines in methylthiouracil-treated rats.
The effect of sodium perchlorate (NaClO4) on the methylthiouracil-induced increase in the activity of thyroid glucose 6-phosphate dehydrogenase (G6PDH), ornithine decarboxylase (ODC) and polyamine contents was studied in the rat. The G6PDH activity was increased nearly three-fold by methylthiouracil (MTU) but not by ClO4- at 7 days of treatment. Perchlorate lowered the MTU-induced enzyme activity to nearly the control level, without changing circulating thyrotrophin (TSH). The anion had no inhibitory effect on G6PDH activity in vitro. The possibility that an inhibitor specific for G6PDH was generated in ClO4- - treated rat thyroids was excluded. The activity of ODC was greatly increased by both ClO4- and MTU, the increase being significant as early as on the second day of treatment. Perchlorate had no inhibitory effect on MTU-induced ODC activity in vivo but decreased total contents of spermidine and spermine in the thyroid, without affecting the concentration (nmoles/g wet weight) of the polyamines. These results suggest that ClO4- acts directly on the thyroid to suppress specifically the stimulatory effect of TSH on G6PDH activity and possibly on polyamine accumulation.
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D008297:Male; D008779:Methylthiouracil / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010472:Perchlorates / Q000494:pharmacology*; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D017670:Sodium Compounds; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood
D013956:Antithyroid Agents; D010472:Perchlorates; D011073:Polyamines; D017670:Sodium Compounds; D013096:Spermine; D012313:RNA; D013972:Thyrotropin; D004247:DNA; C031068:sodium perchlorate; D005954:Glucosephosphate Dehydrogenase; D009955:Ornithine Decarboxylase; D008779:Methylthiouracil; D013095:Spermidine; D011700:Putrescine