Hypothyroxinemia and hypothermia in rats in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin administration.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment on body temperature and serum and tissue levels of thyroid hormones, glucose, glucagon, insulin, and somatostatin were investigated. Within 7 days following TCDD administration (45 micrograms/kg), rats exhibited hypothyroidism compared to pair-fed controls and rats fed ad libitum. Body temperature was maintained in the pair-fed and ad libitum-fed controls but was significantly decreased in TCDD-treated rats at 2 days. Within 2 weeks of the administration of 90 micrograms TCDD/kg, body temperature was below 35 degrees C with the lowest mean value of 34.5 degrees C recorded on Day 16. Mean body temperatures for control rats ranged from 36.8 to 37.5 degrees C. One week after TCDD administration (45 micrograms/kg), serum thyroxine (T4) declined to 46% of pair-fed controls. The decreased free-thyroxine index indicated that the measured decrease in thyroxine reflected decreased hormone concentrations as opposed to altered protein binding. Hypoglycemia occurred in TCDD-treated rats subsequent to hypothyroxinemia and hypothermia, but it did not develop in the pair-fed controls. At 1 week after administration of 45 micrograms TCDD/kg, serum and pancreatic insulin levels were reduced to 25 and 76% of ad libitum-fed controls, respectively. Hypophagia was determined to be responsible for the decreased growth rate and hypoinsulinemia but did not account for hypothyroxinemia, hypothermia, and hypoglycemia following the administration of TCDD. No significant alterations were detected in serum glucagon or in pancreatic, hepatic, or serum somatostatin levels. Decreased somatostatin in the gastric antrum coincided with a 29% increase in stomach dry weight. The delayed toxicity of TCDD may result, in part, from these hormonal alterations.