Induction of steroidogenic enzymes by potassium in cultured rat zona glomerulosa cells depends on calcium influx and intact protein synthesis.
The effects of a calcium channel blocker (nifedipine) and a protein synthesis inhibitor (cycloheximide) on the induction of four steroidogenic cytochromes P450 (CYP11B2, CYP11B1, CYP11A1, and CYP21A1) by an elevated extracellular potassium concentration were studied in cultured rat zona glomerulosa cells. Each of these two pharmacological agents completely inhibited the initiation of CYP11B2 expression and aldosterone biosynthesis in response to a high extracellular potassium concentration (18 mM). They also suppressed the potassium-induced increases in CYP11B1, CYP11A1, and CYP21A1 messenger RNA levels. Increases of these latter parameters elicited by ACTH were also suppressed by cycloheximide but were not affected by nifedipine. According to these experiments, calcium is an important second messenger mediating the effects of a high extra-cellular potassium concentration on the expression of genes encoding steroidogenic enzymes in rat zona glomerulosa cells. Because these effects also depend on an intact protein synthesis, an unknown labile regulatory protein seems to play an important role in the intracellular signal transmission from the plasma membrane to the genome.
Yagci
A
A
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Müller
J
J
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D066246:ErbB Receptors / Q000378:metabolism / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D002121:Calcium Channel Blockers; D007527:Isoenzymes; D011500:Protein Synthesis Inhibitors; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D066246:ErbB Receptors; D009543:Nifedipine; D011188:Potassium; D002118:Calcium