Differences in effects of spironolactone and phenobarbital on the hepatic-thyroid axis in male rats.

Abstract

Treatment with 150mg/kg of spironolactone (SPL) and 100mg/kg of phenobarbital (PB) for 13 weeks increased thyroid weight, numbers of apical vesicles and colloid droplets in thyroid follicular cells, and thyroid follicular hypertrophy. The patterns of elevated serum thyrotropin (TSH) and transiently decreased serum thyroxine (T4) and triiodothyronine (T3) suggest that thyroid follicular hypertrophy is a compensatory reaction to lowered thyroid hormone levels. Treatment with PB or SPL induced increased liver weight, hepatocellular hypertrophy, and smooth endoplasmic reticulum proliferation in hepatocytes. PB-treatment increased Uridine diphosphate glucuronosyl transferase (UDP-GT) activity toward p-nitrophenol and P-450 content but SPL-treatment had no such effect on hepatic microsomal enzymes. PB and SPL have been shown not to directly affect thyroid hormone synthesis. It is concluded that the effect of PB on thyroid function in male rats is secondary to increased hepatic UDP-GT and P-450 and that in SPL-treated male rats a distinct spectrum of isozymes of cytochrome P-450 and UDP-GT and/or other enzymes may play an important role for induction of thyroid hypertrophy.