Cerebellin is a 16-amino acid peptide, originally isolated from rat cerebel
lum, whose presence has been recently demonstrated in the human adrenal gla
nds and especially in medullary chromaffin cells. Cerebellin concentration
dependently increased basal catecholamine (norepinephrine and epinephrine)
release by human adrenal slices, containing medullary chromaffin tissue, mi
nimal and maximal effective concentrations being 10(-9) and 10(-7) mol/L. C
erebellin (10(-7) mol/L) markedly enhanced cAMP release by adrenal slices,
and the protein kinase A inhibitor H-89 (10(-5) mol/L) blocked catecholamin
e response to cerebellin. Cerebellin did not affect basal steroid secretion
of dispersed human adrenocortical cells, but it concentration dependently
increased aldosterone and cortisol production by adrenal slices. Again mini
mal and maximal effective concentrations were 10(-9) and 10(-7) mol/L. Aldo
sterone and cortisol responses to 10(-7) mol/L cerebellin was suppressed by
both the beta-adrenoceptor antagonist l-alprenolol (10(-6) mol/L) and H-89
(10(-5) mol/L). Collectively, the present findings allow us to conclude th
at 1) cerebellin exerts a sizable secretagogue action on both cortex and me
dulla of human adrenals; 2) the peptide directly stimulates catecholamine r
elease via the adenylate cyclase/protein kinase A-dependent signaling pathw
ay; and 3) the mechanism underlying the adrenocortical stimulatory effect o
f cerebellin is indirect and probably involves the release of catecholamine
s, which in turn, acting in a paracrine manner, enhance steroid-hormone sec
retion.