title: Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co-secreting renin and cortisol.
abstract: Abnormal expression of membrane receptors has been previously described in benign adrenocortical neoplasms causing Cushing's syndrome. In particular, we have observed that, in some adreno corticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia tissues, cortisol secretion is controlled by ectopic serotonin(7) (5-HT(7)) receptors. The objective of the present study was to investigate in vitro the effect of serotonin (5-hydroxy tryptamine; 5-HT) on cortisol and renin production by a left adrenocortical carcinoma removed from a 48-year-old female patient with severe Cushing's 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-HT(7) receptor antagonist SB269970. In addition, immunohistochemistry showed the occurrence of 5-HT(7) 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 angiotensin II (Ang II). In conclusion, the present report provides the first demonstration of ectopic serotonin receptors, i.e. 5-HT(7) 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-HT(7) receptors.
authors: INSERM U413, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France.
authors: E
authors: E
authors: Louiset
authors: K
authors: K
authors: Isvi
authors: J M
authors: JM
authors: Gasc
authors: C
authors: C
authors: Duparc
authors: B
authors: B
authors: Cauliez
authors: A
authors: A
authors: Laquerrière
authors: J M
authors: JM
authors: Kuhn
authors: H
authors: H
authors: Lefebvre
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018268:Adrenocortical Carcinoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D003480:Cushing Syndrome / Q000378:metabolism / Q000473:pathology; D005260:Female; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010636:Phenols / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D006728:Hormones; D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; C104425:serotonin 7 receptor; D000804:Angiotensin II; D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D012083:Renin; D006854:Hydrocortisone