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Production and Metabolism of Serotonin (5-HT) by the Human Adrenal Cortex: Paracrine Stimulation of Aldosterone Secretion by 5-HT

European Institute for Peptide Research (IFRMP 23), Department of Endocrinology, INSERM U413, University Hospital of Rouen, (H.L., J.M.K.) 76031 Rouen, France; Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, Unite Associée Centre National de la Recherche Scientifique, University of Rouen, (H.L., V.C., C.D., H.V., J.M.K.) 76821 Mont-Saint-Aignan, France; and Department of Pharmacology, INSERM E 9920, University Hospital of Rouen, (P.C., C.T.) 76031 Rouen, France

Address all correspondence and requests for reprints to: Dr. Hervé Lefebvre, IFRMP 23, Department of Endocrinology, INSERM U413, Hospital of Boisguillaume, University Hospital of Rouen, 76031 Rouen cedex, France. E-mail: herve.lefebvre{at}chu-rouen.fr

Abstract

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-HT₄ 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.

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