Effects of adrenomedullin on the human adrenal glands: an in vitro study

Numerous lines of evidence indicate that adrenal medulla exerts a paracrine control on the secretory activity of the cortex by releasing catecholamines and several regulatory peptides. Adrenomedullin (ADM) is contained in adrenal medulla of several mammalian species, including humans. Thus, we investigated whether human ADM1-52 exerts a modulatory action on steroid secretion of human adrenal cortex in vitro. Dispersed adrenocortical cells (obtained from the gland tail deprived of chromaffin cells) and adrenal slices (including both capsule and medulla) were employed. ADM specifically inhibited angiotensin II-stimulated aldosterone secretion of dispersed cells and enhanced basal aldosterone production by adrenal slices, minimal effective concentrations being 10(-7) and 10(-9) mol/L, respectively. These effects of ADM were suppressed by the CGRP1 receptor antagonist CGRP8-37 (10(-5) mol/L). Neither basal and ACTH-stimulated aldosterone secretion of dispersed cells nor agonist-enhanced aldosterone production by adrenal slices were affected by ADM, which also did not alter cortisol secretion of both types of adrenal preparations. ADM (10(-6) mol/L) blunted the aldosterone secretagogue action of the Ca2+ ionophore A23187 (10(-5) mol/L) on dispersed cells and adrenal slices. The beta-adrenoceptor antagonist l-alprenolol (10(-6) mol/L) suppressed aldosterone response of adrenal slices to 10(-7) mol/L isoprenaline and ADM. ADM concentration dependently raised epinephrine and norepinephrine release by adrenal slices, minimal effective concentration being 10(-9) mol/L. Collectively, these findings suggest that ADM, acting via the CGRP1 receptor subtype, exerts a direct inhibitory effect on angiotensin II-stimulated aldosterone secretion, which, when the integrity of adrenal tissue is preserved, is overcome and reversed by an indirect stimulatory action, conceivably involving the release of catecholamines by adrenal chromaffin cells.