An update on the role of phospholipid metabolism in the action of steroidogenic agents.
Most steroidogenic agents which bind to cell surface receptors activate adenylate cyclase and/or phospholipase C. Activation of either signaling system may also be associated with rapid increases in de novo phospholipid synthesis, but it is at present uncertain whether this is a secondary or parallel event. Activation of phospholipase C leads to hydrolysis of phosphatidylinositol-4',5'-PO4 (PIP2) and generation of two second messengers, inositol-triphosphate and diacylglycerol (DAG), which mobilize Ca2+ and activate protein kinase C, respectively. Increases in de novo phospholipid synthesis lead to rapid increases in phosphatidic acid, DAG and C-kinase activity. The PIP2-phospholipase C system appears to initiate the steroidogenic response to certain agents, such as angiotensin-II, and this may be amplified by concomitant increases in phospholipid synthesis. With other agonists, the role of phospholipase C activation and de novo phospholipid (and DAG) synthesis is less certain. In some tissues, activation of protein kinase C by exogeneously added DAG analogues provokes an increase in steroidogenesis. However, this is not observed in other tissues, and it is uncertain whether this rules out involvement of the C-kinase system for steroidogenesis in these tissues, or whether endogenously produced DAG is a more effective activator of the relevant C-kinase system then exogenously added DAG analogues. The role of other potential intracellular signaling substances that may be derived from phospholipase C activation and de novo phospholipid synthesis is also at present uncertain, as are the interrelationships between these two phospholipid responses, cyclic nucleotides, and other steroidogenic factors.
Farese
R V
RV
Veterans Administration Hospital, Tampa, FL.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D004075:Diglycerides / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D010716:Phosphatidylinositols / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D004075:Diglycerides; D010716:Phosphatidylinositols; D010743:Phospholipids; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases