Effect of Thyroid Hormones on Metabolism of d,l-Norepinephrine by Isolated Rat Liver

The effect of thyroid hormones and antithyroid agents on the hepatic metabolism of exogenous d,l-norepinephrine-7-¹⁴C (NE) was studied in isolated perfused livers. No direct effect of l-thyroxine could be demonstrated. However, mild hyperthyroidism in the liver-donor rats led to increased metabolism of administered NE, with increased excretion of normetanephrine glucuronide (NMET-G) in the bile and accumulation of this metabolite in the blood, indicating increased activities of catechol O-methyl transferase (COMT) and glucuronyl transferase. Mild hypothyroidism, induced in liver donors with propylthiouracil or radioiodine, led to decreased metabolism of administered NE and slight decreases in the production of NMET-G and 3-methoxy-4-hydroxyphenylglycol sulfate (MHPG-S) and decreased excretion of these metabolites in bile, indicating possible decreases i n the activities of COMT and monoamine oxi-dase (MAO) as well as in conjugating enzymes. Propylthiouracil appeared to inhibit conjugation, as shown by the accumulation of uncon-jugated metabolites in the blood. Circulating NE disappeared rapidly from the perfusate during perfusion of the liver regardless of alterations i n thyroid status of liver-donor rats. (Endocrinology80: 808, 1967)