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E Louiset, INSERM U413, University of Rouen, Mont saint Aignan, France
K Isvi, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Department of Endocrinology, Rouen, France
J Gasc, College de France, INSERM U833, Paris, France
C Duparc, INSERM U413, University of Rouen, Mont saint Aignan, France
B Cauliez, Laboratory of Biochemistry, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Rouen, France
A Laquerriere, Department of Pathology, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Rouen, France
J Kuhn, Department of Endocrinology, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Rouen, France
H Lefebvre, Department of Endocrinology, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Rouen, France

Correspondence: Estelle Louiset, Email: estelle.louiset{at}univ-rouen.fr

Abstract

Abnormal expression of membrane receptors has been previously described in benign adrenocortical neoplasms causing Cushings syndrome. In particular, we have observed that, in some ACTH-independent macronodular adrenal hyperplasia tissues, cortisol secretion is controlled by ectopic serotonin 7 (5-HT7) receptors. The objective of the present study was to investigate in vitro the effect of serotonin (5-HT) on cortisol and renin production by a left adrenocortical carcinoma removed from a 48-yr-old female patient with severe Cushings syndrome and elevated plasma renin levels. Tumor explants were obtained at surgery and processed for immunohistochemistry, in situ hybridization and cell culture studies. 5-HT-like immunoreactivity was observed in mast cells and steroidogenic cells disseminated in the tissue. 5-HT stimulated cortisol release by cultured cells. The stimulatory effect of 5-HT on cortisol secretion was suppressed by the 5-HT7 receptor antagonist SB269970. In addition, immunohistochemistry showed the occurrence of 5-HT7 receptor-like immunoreactivity in carcinoma cells. mRNAs encoding renin as well as renin-like immunoreactivity were detected in endothelial and tumor cells. Cell incubation studies revealed that the adrenocortical tissue also released renin. Renin production was inhibited by 5-HT but was not influenced by ACTH and AngII. In conclusion, the present report provides the first demonstration of ectopic serotonin receptors, i.e. 5-HT7 receptors, in an adrenocortical carcinoma. Our results also indicate that 5-HT can influence the secretory activity of malignant adrenocortical tumors in an autocrine/paracrine manner. The effects of 5-HT on adrenocortical tumor cells included a paradoxical inhibitory action on renin production and a stimulatory action on cortisol secretion involving 5-HT7 receptors.