The influence of cortisol on the enzymes of fatty acid synthesis in developing mammalian lung and brain.
Administration of cortisol to fetal rabbits resulted in a 42% inhibition of pulmonary de novo fatty acid synthesis from acetyl coenzyme A (CoA) (P = less than 0.025). This was associated with inhibition of acetyl-CoA carboxylase (EC. 6.4.1.2.) activity (P = less than 0.01) and a tendency towards decreased activity of fatty acid synthetase. There was no effect on pulmonary microsomal fatty acid elongation activity. Light and electron microscopic examination of the apex of the right lung of control and cortisol-treated animals revealed changes consistent with accelerated lung maturation in the treated animals. The in vitro activities of acetyl-CoA carboxylase and fatty acid synthetase were similar in rabbit lung and thus acetyl-CoA carboxylase activity does not appear to be rate limiting for de novo fatty acid synthesis in lung. No significant change in the activity of enzymes associated with de novo fatty acid synthesis of microsomal fatty acid elongation was found in fetal brain after cortisol exposure. However, in a parallel study on fatty acid synthesis in fetal liver, cortisol administration resulted in a 30% increase in fatty acid synthetase activity (P less than 0.025). The finding of cortisol-induced inhibition of de novo fatty acid synthesis in fetal rabbit lung may be related to the known inhibitory effect of cortisol on lung growth in the fetus.
D000105:Acetyl Coenzyme A / Q000037:antagonists & inhibitors; D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000254:growth & development; D003065:Coenzyme A / Q000031:analogs & derivatives*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D005227:Fatty Acids / Q000096:biosynthesis; D005333:Fetus / Q000032:analysis; D006128:Growth / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology*; D008025:Ligases / Q000037:antagonists & inhibitors*; D008099:Liver / Q000254:growth & development; D008168:Lung / Q000254:growth & development / Q000648:ultrastructure; D008861:Microsomes / Q000032:analysis; D008862:Microsomes, Liver / Q000032:analysis; D011817:Rabbits
D005227:Fatty Acids; D000105:Acetyl Coenzyme A; D064429:Fatty Acid Synthases; D008025:Ligases; D000103:Acetyl-CoA Carboxylase; D003065:Coenzyme A; D006854:Hydrocortisone