Effects of adrenomedullin and proadrenomedullin N-terminal 20 peptide on steroid production in dispersed rat adrenal zona glomerulosa cells

Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two hypotensive peptides, contained in adrenal medulla, which are able to inhibit aldosterone secretion from zona glomerulosa. In this study we have compared the effects of the two peptides on the production of post-pregnenolone steroids by dispersed rat zona glomerulosa cells. ADM and PAMP did not alter basal steroid secretion. Conversely, they inhibited angiotensin-II (10(-9) M)-stimulated 18-hydroxy-11-deoxycorticosterone, corticosterone, 18-hydroxycorticosterone and aldosterone production, without affecting progesterone and 11-deoxycorticosterone secretion. PAMP was significantly more effective than ADM, their minimal effective concentrations being 10(-10) M and 10(-8)-10(-7) M, respectively. ADM, but not PAMP markedly lowered either basal and agonist-enhanced release of 11-dehydrocorticosterone. Collectively, these findings allow us to draw the following conclusions: (i) ADM and PAMP electively inhibit 11 beta-hydroxylase and aldosterone synthase, PAMP being probably to be considered the proadrenomedullin-derived physiological inhibitor of mineralocorticoid secretion in rats; and (ii) ADM, but not PAMP, also exerts a clear-cut inhibitory action on 11 beta-hydroxysteroid dehydrogenase, the enzyme that converts corticosterone to its inactive form.