title: Hormonal control of pulmonary surfactant synthesis.
abstract: The specific activities of palmitoyl-CoA synthetase, phospholipase A2, and lysophosphatidylcholine acyltransferase enzymes were low in the lungs of diabetic and hypophysectomized rats as compared to those found in the normal controls. Administration of triiodothyronine (T3), to the diabetic and hypophysectomized rats restored the normal activities of these enzymes. Stimulation of the enzyme activities were also observed when normal rats were injected with the above hormone. The enhancement of the enzyme activities was also found to be dependent on the dose and duration of the hormonal treatment. Optimum levels were achieved at a dose of about 100 micrograms/100 g body weight of T3, 3-4 days after the administration of this hormone. Actinomycin D or cycloheximide abolished the hormone-mediated stimulation of these enzymes in diabetic and hypophysectomized rats. Reduced rate of in vivo palmitoyl-CoA synthetase synthesis was observed in the lungs of diabetic and hypophysectomized animals. Administration of T3 stimulated the rate of synthesis of this enzyme indicating increasing synthesis of this enzyme and not of activation of the pre-existing inactive species. Reduced phospholipid contents, specially decreased amount of lecithin and dipalmitoyl lecithin (DPL) were observed in the lungs of the diabetic and hypophysectomized animals as compared to those in the normal animals. T3 also increased the lecithin and DPL content of the normal rat lungs. These results provide evidence for the involvement of the thyroid hormones in the control of the pulmonary surfactant. The results further suggest that T3 was capable of inducing the enzymes of the "deacylation-reacylation" pathway involved in palmitate incorporation into phosphatidylcholine thereby contributing to the stimulation of dipalmitoyl phosphatidylcholine biosynthesis.
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D008168:Lung / Q000201:enzymology*; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014284:Triiodothyronine / Q000494:pharmacology*; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D007328:Insulin; D011663:Pulmonary Surfactants; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014284:Triiodothyronine; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D010741:Phospholipases A; D054467:Phospholipases A2; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase