Thyroid hormone regulation of heme synthesis in rat liver

Thyroid hormone alters the rate of heme degradation and the levels of cytochrome P450 in rat liver. These studies report the effects of thyroid status on the activity of hepatic delta-aminolevulinate synthase (ALAS), the initial and rate-limiting enzyme in heme synthesis. Thyroidectomized male Sprague-Dawley rats received sc injections of diluent or hormones. T3 was found to stimulate ALAS activity in the liver in doses which rendered the animals euthyroid (0.3 microgram/100 g BW.day). Higher doses failed to enhance enzyme activity further. T4 had similar effects but was less potent; rT3 had no effect on ALAS activity. The administration of a large single dose of T3 (50 micrograms/100 g BW) produced a significant (P less than 0.001) increase in ALAS activity 72 h later. Allylisopropylacetamide administration induced ALAS activity to identical levels in both hypothyroid and T3-replaced animals when administered at a dose of 200 mg/kg body wt. A dose of 400 mg/kg body wt allylisopropylacetamide, one associated with maximal induction of ALAS, resulted in an 80% higher enzyme activity in T3-treated animals compared with controls. Exogenous T3 had no effect on ALAS activity in sham-operated animals. These findings indicate that thyroid status can influence the activity of ALAS, the rate-limiting enzyme in the synthesis of heme in rat liver, as well as heme degradation and the content of cytochrome P450 in this organ.