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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.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-01929382
Contributor : Céline Duparc <>
Submitted on : Wednesday, November 21, 2018 - 10:44:27 AM
Last modification on : Wednesday, September 23, 2020 - 4:34:42 AM

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Estelle Louiset, Karine Isvi, Jm Gasc, Céline Duparc, Bruno Cauliez, et al.. Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co-secreting renin and cortisol. Endocrine-Related Cancer, BioScientifica, 2008, 15 (4), pp.1025 - 1034. ⟨10.1677/ERC-08-0085⟩. ⟨hal-01929382⟩

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