EFFECTS OF ADRENOMEDULLIN AND PROADRENOMEDULLIN N-TERMINAL-20 PEPTIDEON 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 ar e able to inhibit aldosterone secretion from zona glomerulosa. In this study we have compared the effects of the two peptides on the product ion of post-pregnenolone steroids by dispersed rat zona glomerulosa ce lls. ADM and PAMP did not alter basal steroid secretion. Conversely, t hey inhibited angiotensin-II (10(-9) M)-stimulated 18-hydroxy-11-deoxy corticosterone, corticosterone, 18-hydroxycorticosterone and aldostero ne production, without affecting progesterone and 11-deoxycorticostero ne secretion. PAMP was significantly more effective than ADM, their mi nimal effective concentrations being 10(-10) M and 10(-8)-10(-7) M, re spectively. ADM, but not PAMP markedly lowered either basal and agonis t-enhanced release of 11-dehydrocorticosterone. Collectively, these fi ndings allow us to draw the following conclusions: (i) ADM and PAMP el ectively inhibit 11 beta-hydroxylase and aldosterone synthase, PAMP be ing probably to be considered the proadrenomedullin-derived physiologi cal inhibitor of mineralocorticoid secretion in rats; and (ii) ADM, bu t not PAMP, also exerts a clear-cut inhibitory action on 11 beta-hydro xysteroid dehydrogenase, the enzyme that converts corticosterone to it s inactive form.