Effects of Phenobarbital on Hypothalamic-Pituitary-Thyroid Axis in the Rat

Abstract

It has been reported that phenobarbital (PB) increases the peripheral clearance of T4 and T3 and decreases serum T4 and T3 concentrations in the rat, but serum TSH remains unchanged. To explore a possible direct effect of PB on TSH secretion at the hypothalamic-pituitary level, adult male rats were given PB 100 mg/kg or vehicle IP for 10 days. No difference in their thyroid weights was observed. In the PB-treated group serum T4 was decreased (PB, 3 +/- 0.2 micrograms/dl vs. control, 3.8 +/- 0.1 micrograms/dl, mean +/- SE, p less than .002), as was serum T3 (PB, 51 +/- 6 ng/dl vs. control, 70 +/- 5 ng/dl, p less than .05), but serum TSH remained unchanged. Pituitary TSH and hypothalamic TRH contents also were unchanged. Further studies were carried out similarly in the thyroidectomized hypothyroid rat to eliminate the effect of PB on serum T4 and T3 levels. PB or vehicle were started two days after thyroidectomy. By postoperative day 12, TSH levels in the PB-treated rats were lower than in the controls (PB, 697 +/- 62 microU/ml vs. control, 891 +/- 53 microU/ml, p less than .05). Pituitary TSH and hypothalamic TRH contents again were similar in both groups. When TRH (500 ng/kg body weight, IV) was given, the increment in serum TSH at 10 minutes was significantly lower in the PB group (PB, 53 +/- 26 microU/ml vs. control, 131 +/- 18 microU/ml, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)