EFFECTS OF ADRENOMEDULLIN ON THE HUMAN ADRENAL-GLANDS - AN IN-VITRO STUDY

Numerous lines of evidence indicate that adrenal medulla exerts a para crine control on the secretory activity of the cortex by releasing cat echolamines and several regulatory peptides. Adrenomedullin (ADM) is c ontained in adrenal medulla of several mammalian species, including hu mans. Thus, we investigated whether human ADM1-52 exerts a modulatory action on steroid secretion of human adrenal cortex in vitro. Disperse d adrenocortical cells (obtained from the gland tail deprived of chrom affin cells) and adrenal slices (including both capsule and medulla) w ere employed. ADM specifically inhibited angiotensin II-stimulated ald osterone secretion of dispersed cells and enhanced basal aldosterone p roduction by adrenal slices, minimal effective concentrations being 10 (-7) and 10(-9) mol/L, respectively. These effects of ADM were suppres sed 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 affect ed by ADM, which also did not alter cortisol secretion of both types o f adrenal preparations. ADM (10(-6) mol/L) blunted the aldosterone sec retagogue action of the Ca2+ ionophore A23187 (10(-5) mol/L) on disper sed cells and adrenal slices. The p-adrenoceptor antagonist I-alprenol ol (10(-6) mol/L) suppressed aldosterone response of adrenal slices to 10(-7) mol/L isoprenaline and ADM. ADM concentration dependently rais ed epinephrine and norepinephrine release by adrenal slices, minimal e ffective concentration being 10(-9) mol/L. Collectively, these finding s suggest that ADM, acting via the CGRP1 receptor subtype, exerts a di rect inhibitory effect on angiotensin II-stimulated aldosterone secret ion, which, when the integrity of adrenal tissue is preserved, is over come and reversed by an indirect stimulatory action, conceivably invol ving the release of catecholamines by adrenal chromaffin cells.