ROLE OF THYROID-HORMONE IN DE-NOVO SYNTHESIS OF CHOLINEPHOSPHOTRANSFERASE IN GUINEA-PIG LUNG MITOCHONDRIA AND MICROSOMES

It is known that thyroid hormone enhances the biosynthesis of Phosphatidylcholine in the lung. The purpose of the present study was to investigate the effects of thyroid hormone on the activity of cholinephosphotransferase, the terminal enzyme in the CDP-choline pathway, in guinea pig lung mitochondria and microsomes. Intramuscular injection of triiodothyronine (T3, 0.25-4 mg/kg body wt) stimulated the activities of both mitochondrial and microsomal enzymes in a dose-dependent manner. However, the stimulation was much more pronounced in the microsomes than in the mitochondria. The stimulatory effect of T3 was blocked by the intraperitoneal injection of both actinomycin D and cycloheximide in the microsomes, whereas in the mitochondria, the hormonal effect was blocked only by cycloheximide. Thus, it is suggested that T3 stimulates not only the nucleocytoplasmic system for the de novo synthesis of the enzyme, but possibly also the regulation of the transport of the synthesized protein into the mitochondria. Furthermore, administration of T3 produced an increase in the uptake and incorporation of [C-14]choline into phospholipids of lung slices in vitro. However, this effect was blocked by intraperitoneal injection of both actinomycin D and cycloheximide. Thus, the change in CPT activity by T3 in mitochondria is not reflected by enhanced incorporation of choline into phosphatidylcholine.