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 cells, and we have shown that 5-HT stimulates aldosterone secretion, suggesting that 5-HT may control glomerulosa cells through a paracrine mechanism. Concurrently, the presence of 5-hydroxyindolacetic acid in human adrenocortical extracts indicates that 5-HT may be metabolized after local release by mast cells. The aim of the present study was to investigate in vitro the production and metabolism of 5-HT by the human adrenal cortex. Perifused adrenal 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 induced a burst of 5-HT secretion followed by a gradual increase in aldosterone production. Administration of the specific 5-HT(4) receptor antagonist GR 113808 (10(-6) M) did not affect compound 48/80-induced 5-HT release but abolished the stimulatory effect of compound 48/80 on aldosterone secretion, indicating 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) provoked the formation of the 5-HT metabolite 5-hydroxytryptophol. The type A monoamine oxidase (MAO) inhibitor clorgyline (10(-6) M) suppressed the metabolism of 5-HT into 5-hydroxytryptophol. Immunocytochemical staining of cultured 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, immunohistochemical 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 paracrine manner. Our data also indicate that 5-HT is metabolized by MAO-A located in intracortical chromaffin cells.