Stimulation of liver mitochondrial alpha-glycerophosphate dehydrogenase activity by L-thyroxine in thyroidectomized rats: comparison with the suppression of pituitary TSH secretion.

The rate of liver mitochondrial alpha-glycerophosphate dehydrogenase (GPD) induction was compared to the suppression of pituitary thyrotropin (TSH) secretion in thyroidectomized rats submitted to prolonged administration of small amounts of L-thyroxine (T4). With both 350 and 530 ng T4/100 g bw/day, liver alpha-GPD activity remained at post-thyroidectomy level (mean +/- SE: 0.030 +/- 0.002 and 0.034 +/- 0.001 delta A/mg prot/min, respectively) throughout all experiment. A sharp increase in enzyme activity was observed after 3 weeks of treatment in rats receiving 715 ng T4 / 100 g bw / day (mean +/- SE: 0.086 +/- 0.003 delta A/mg prot/min). In contrast, serum TSH levels were lower than pretreatment values (199 +/- 8ng/dI) in rats receiving 350 ng T4/100 g bw/day (mean +/- SE: 104 +/- 15 ng/dI; t = 7.48, p less than 0.001), decreased progressively with increasing T4 doses (m +/- SE:530 ng T4/100 g/day = 36 +/- 7 ng/dI); after only 48 h of treatment and were not significantly modified thereafter. The data are in agreement with the hypothesis of a nonlinear relationship between the degree of thyroid hormone receptor occupancy and the rate of liver mitochondrial alpha-GPD induction.