Inhibition of aldosterone synthesis by atrial natriuretic factor.
Atrial natriuretic factor (ANF) inhibits basal and stimulated aldosterone synthesis in adrenal glomerulosa cells. ANF probably acts through specific membrane receptors. Alterations in cyclic GMP and cyclic AMP levels do not account for ANF's inhibitory effect. ANF does not block angiotensin II (AngII) receptors nor does it interfere with phosphoinositide metabolism or calcium movements stimulated by adrenal agonists. ANF does not inhibit protein synthesis nor does it work by inhibiting NA+,K+-ATPase or depleting cell potassium. ANF decreases conversion of endogenous cholesterol to pregnenolone, the step stimulated by adrenocorticotropin and AngII. ANF does not affect the conversion of 20-alpha-hydroxycholesterol, which easily penetrates mitochondrial membranes to the site of the cholesterol side-chain cleavage enzyme. These results suggest that ANF inhibits the ability of endogenous cholesterol to reach or interact with the side-chain cleavage enzyme. ANF does not act like a calcium channel-blocking agent. However, ANF is less effective at high-calcium concentrations, which suggests that it may inhibit a step that calcium stimulates. Understanding ANF action will probably require identification of the specific biochemical changes (mediators) that it induces. Parallel efforts to understand how other agents stimulate steroidogenesis (particularly in the areas of protein synthesis, protein phosphorylation, and cholesterol movements) will further this understanding.
D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000032:analysis; D006152:Cyclic GMP / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000378:metabolism; D014176:Protein Biosynthesis; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000032:analysis; D013329:Structure-Activity Relationship
D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D002118:Calcium