The Roles of Potassium and Corticosteroids in Determining the Pattern of Metabolism of [3H]Deoxycorticosterone by Monolayer Cultures of Rat Adrenal Zona Glomerulosa Cells

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Abstract
The metabolism of [3H]deoxycorticosterone (DOC) by primary monolayer cultures of rat adrenal zona glomerulosa cells was studied under various conditions. The cells converted [3H]DOC to aldosterone, 18-hydroxycorticosterone (18OH-B), corticosterone and 18-hydroxydeoxycorticosterone (18OH-DOC). When the K concentration of the culture medium was 8, 12, 18 or 40 mM the pattern of metabolism of [3H]DOC was glomerulosa-like, i.e., the major products were aldosterone and 18OH-B with corticosterone and 18OH-DOC being minor metabolites. Treatment of the cells with 40 mM K+ resulted in a pattern of [3H]DOC metabolism where aldosterone and 18OH-B accounted for > 90% of the metabolites of the radioactive precursor; 18OH-DOC was nearly undetectable. This pattern was maintained by raised K+ levels for at least 28 days, the duration of the experiments. With culture medium containing 4 mM K+, however, the pattern became fasciculata-like; corticosterone and 18OH-DOC were the major products with little aldosterone or 18OH-B. The addition of 20 or 500 .mu.M, but not 1 .mu.M, monobutyryl cyclic[c]AMP to glomerulosa cultures converted the glomerulosa-like pattern of [3H]DOC metabolism to the fasciculata-like, as did also 55 .mu.M corticosterone, cortisol, 18OH-DOC, but not 55 .mu.M aldosterone. The effects of these corticosteroids suggest that they may mediate the action of monobutyryl cAMP. Since this cAMP derivative did not reproduce the effects of high K+ on the pattern of [3H]DOC metabolism, it is probable that this long-term action of K+ on the glomerulosa cell is not mediated by intracellular cAMP. Instead, there may be an important regulatory mechanism in the function of the glomerulosa cell which is directly sensitive to the intracellular K+ level and is inhibited by glucocorticoids. These characteristics suggest that this control point may involve protein synthesis.