The mechanism of the effect of K + on the steroidogenesis of rat zona glomerulosa cells of the adrenal cortex: role of cyclic AMP

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Abstract
The effects of various concentrations of extracellular K + (3.6 - 13 mM) on the steroid (corticosterone and aldosterone) and cyclic AMP outputs of capsular cells (95% zona glomerulosa) of the rat adrenal cortex were studied at different concentrations of extracellular Ca 2+ . Small amounts of EGTA (50 μM) were added to reduce the free Ca 2+ concentrations effectively to zero at the lowest possible total Ca 2+ concentration. At a total extracellular concentration of 2.5 mM Ca 2+ , in 27 experiments the mean values of the steroid and cAMP outputs showed a maximum at 8.4 mM K + . The increase in steroid and cAMP outputs at 5.9, 8.4 and 13 mM K + compared with that at 3.6 mM were highly significant ( p < 0.01). The overall correlation of either corticosterone or aldosterone with cAMP outputs was also highly significant and was even better from 3.6 to 8.4 mM K + . Lowering the effective free concentration of Ca 2+ to zero decreased the steroid and cAMP outputs significantly at all K + concentrations, and no output was then significantly higher than at 3.6 mM. With the pooled data on outputs at all total Ca 2+ (2.5, 0.5, 0.25, 0.10, 0.05 and 0.0 mM) and K + (3.6, 5.9, 8.4 and 13 mM) concentrations, the correlation of either steroid with cAMP outputs was highly significant (but again optimally from 3.6 to 8.4 mM K + ). Nifedipine (10 -6 to 10 -4 M) was added to the incubations with the aim of specifically inhibiting Ca 2+ influx at total extracellular Ca 2+ concentra­tions of 2.5, 1.25 and 0.25 mM and with the usual K + concentrations. The cAMP outputs were reduced at all K + concentrations above 3.6 mM K + . The effect was highly significant at 10 -4 M nifedipine and a total Ca 2+ of 1.25 mM, which with the incubation conditions used, corresponds to the free Ca 2+ concentrations in vivo . These results indicate that cAMP plays a significant role in the stimulation of steroid output by K + particularly between 3.6 and 8.4 mM K + . In this range of K + concentrations the stimulation of cAMP seems to be controlled by increases in Ca 2+ influx. The correlation of steroid and cAMP output at the higher K + concentra­tions (between 8.4 and 13 mM K) and at the various total Ca 2+ concentra­tions is less significant. Also, with all concentrations of added nifedipine there is an ‘anomalous’ increase in steroid output at 13 mM K + and at total Ca 2+ concentrations of 2.5 and 1.25 mM. However, at the same K + concentrations and at 0.25 mM Ca 2+ , nifedipine decreases steroid outputs. Our previous data, obtained after addition of maximally effective amounts of cAMP, indicated that there were also non-cAMP mechanisms involved in the stimulation of steroidogenesis by K + in z. g. cells. The present data confirm this conclusion, particularly at K + concentrations above 8.4 mM. They also indicate that at these higher K + concentrations, by non-cAMP mechanisms increasing intracellular Ca 2+ concentrations probably inhibit steroidogenesis. We conclude, however, that in the physiological range of K + concentra­tions, the role of cAMP in zona glomerulosa cells is at least comparable in importance to that of non-cAMP mechanisms.
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