Adrenocorticotropin and adenosine 3',5'-monophosphate stimulate de novo synthesis of adrenal phosphatidic acid by a cycloheximide-sensitive, CA++-dependent mechanism.
We tested further our postulate that enhanced de novo synthesis of phosphatidic acid is responsible for ACTH- and cAMP-induced increases in adrenal phospholipids in the phosphatidate polyphosphoinositide pathway. During incubation of adrenal sections or cells in vitro, ACTH and cAMP increased the concentrations of and incorporation of [3H]glycerol and [14C]palmitate into phosphatidylcholine and phosphatidylethanolamine, two major phospholipids which are derived from phosphatidic acid, but are extrinsic to the inositide pathway. Thus, it is unlikely that ACTH and cAMP increase inositide phospholipids at the expense of other phospholipids. Similar to previously reported effects on phosphatidic acid and inositide phospholipids, cycloheximide blocked the effects of ACTH and cAMP on phosphatidylcholine and phosphatidylethanolamine. In addition, Ca++ was required for these effects, as well as for cAMP-induced increases in phosphatidic acid, inositide phospholipids, and steroidogenesis. Our findings strongly suggest that ACTH, via cAMP, stimulates de novo phosphatidate synthesis by a cycloheximide-sensitive, Ca++-dependent process, and this stimulation causes a rapid generalized increase in adrenal phospholipids. Moreover, the increased incorporation of labeled glycerol and palmitate into phospholipids suggests that ACTH and cAMP may stimulate the glycerol-3'-PO4 acyltransferase reaction. This stimulatory effect may play a central role in the steroidogenic and trophic actions of ACTH and cAMP.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003345:Corticosterone / Q000096:biosynthesis; D000242:Cyclic AMP / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D010712:Phosphatidic Acids; D010743:Phospholipids; D014316:Tritium; D000324:Adrenocorticotropic Hormone; D003513:Cycloheximide; D000242:Cyclic AMP; D005990:Glycerol; D002118:Calcium; D003345:Corticosterone