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 sy nthesis inhibitor (cycloheximide) on the induction of four steroidogen ic cytochromes P450 (CYP11B2, CYP11B1, CYP11A1, and CYP21A1) by an ele vated extracellular potassium concentration were studied in cultured r at zona glomerulosa cells. Each of these two pharmacological agents co mpletely inhibited the Initiation of CYP11B2 expression and aldosteron e biosynthesis in response to a high extracellular potassium concentra tion (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 cyclohexim ide but were not affected by nifedipine. According to these experiment s, calcium is an important second messenger mediating the effects of a high extracellular 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 intra cellular signal transmission from the plasma membrane to the genome.