Studies on the intracellular mechanism of action of α-melanocyte-stimulating hormone on rat adrenal zona glomerulosa

in Journal of Molecular Endocrinology
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The intracellular mechanisms of action of α-MSH in rat adrenocortical cells were examined. When rat adrenal capsule (largely glomerulosa) cells were stimulated with a range of concentrations of α-MSH there was significant stimulation of aldosterone secretion at 10-10 mol/l, although cyclic AMP was not increased until high concentrations of α-MSH were used (10-6 mol/l and above). However, cells incubated with ACTH showed an increase in aldosterone secretion at 10-11 mol/l and levels of cyclic AMP were elevated at 10-9 mol ACTH/1.

When rat adrenal whole capsules were incubated with α-MSH, membrane-bound protein kinase C (PKC) activity was increased and cytosolic enzyme activity decreased, showing PKC activation. Stimulation with angiotensin II also induced translocation of PKC activity, but ACTH did not.

When [3H]inositol-loaded glomerulosa cells were stimulated with α-MSH there was significant generation of [3H]inositol trisphosphate (IP3) at concentrations of α-MSH which stimulated secretion of aldosterone. Significantly increased levels of [3H]IP3 were also measured when loaded cells were exposed to angiotensin II. ACTH did not cause any significant stimulation of [3H]IP3 production at any concentration used. These results indicate that activation of PKC and phospholipase C is important in modulating the steroidogenic effect of α-MSH.


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