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 Phosphat idylcholine in the lung. The purpose of the present study was to inves tigate the effects of thyroid hormone on the activity of cholinephosph otransferase, the terminal enzyme in the CDP-choline pathway, in guine a pig lung mitochondria and microsomes. Intramuscular injection of tri iodothyronine (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 th an in the mitochondria. The stimulatory effect of T3 was blocked by th e 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 stimulate s not only the nucleocytoplasmic system for the de novo synthesis of t he enzyme, but possibly also the regulation of the transport of the sy nthesized protein into the mitochondria. Furthermore, administration o f T3 produced an increase in the uptake and incorporation of [C-14]cho line into phospholipids of lung slices in vitro. However, this effect was blocked by intraperitoneal injection of both actinomycin D and cyc loheximide. Thus, the change in CPT activity by T3 in mitochondria is not reflected by enhanced incorporation of choline into phosphatidylch oline.