Production and metabolism of serotonin (5-HT) by the human adrenal cortex:Paracrine stimulation of aldosterone secretion by 5-HT

In the human adrenal cortex, serotonin (5-HT) is contained in mast-like cel ls, and we have shown that 5-HT stimulates aldosterone secretion, suggestin g that 5-HT may control glomerulosa cells through a paracrine mechanism. Co ncurrently, the presence of 5-hydroxyindolacetic acid in human adrenocortic al extracts indicates that 5-HT may be metabolized after local release by m ast cells. The aim of the present study was to investigate in vitro the pro duction and metabolism of 5-HT by the human adrenal cortex. Perifused adren al slices released spontaneously detectable amounts of 5-HT (0.74 +/- 0.38 fmol/mg wet tissue-min). The mast cell-depleting drug compound 48/80 induce d a burst of 5-HT secretion followed by a gradual increase in aldosterone p roduction. Administration of the specific 5-HT4 receptor antagonist GR 1138 08 (10(-6) M) did not affect compound 48/80-induced 5-HT release but abolis hed the stimulatory effect of compound 48/80 on aldosterone secretion, indi cating that 5-HT released locally is responsible for a paracrine control of steroidogenesis. Incubation of cells from the human adrenal cortex with 5-HT (10(-5) M) prov oked the formation of the 5.HT metabolite 5-hydroxytryptophol. The type A m onoamine oxidase (MAO) inhibitor clorgyline (10(-6) M) suppressed the metab olism of 5-HT into 5-hydroxytryptophol. Immunocytochemical staining of cult ured cells revealed the presence of a subpopulation of MAO-A-positive cells . Double labeling with an antiserum against chromogranin A showed that MAO- A was actually contained in chromaffin cells. Similarly, immunohistochemica l staining of adrenal slices showed that MAO-A was expressed in chromaffin cells located both in the medulla and in intracortical rays. In conclusion, the present study shows that, in the human adrenal cortex, 5 -HT, released by mast-cells, may stimulate aldosterone secretion in a parac rine manner. Our data also indicate that 5-HT is metabolized by MAO-A locat ed in intracortical chromaffin cells.