Expression profile of serotonin4 (5-HT4) receptors in adrenocortical aldosterone-producing adenomas.
OBJECTIVE
We aimed to investigate the expression profile of serotonin4 (5-HT4) receptors in adrenocortical aldosterone-producing adenoma (APA) tissues in comparison with normal adrenal cortex.


METHODS
Total 5-HT4 receptor mRNAs were quantified by real-time quantitative polymerase chain reaction (PCR) assay, and the mRNAs encoding the 5-HT4 receptor isoforms were characterized by reverse transcription (RT)-PCR in seven normal adrenal cortices and 11 APA tissues. The distribution of 5-HT4 receptor mRNAs was investigated by in situ hybridization in both normal adrenal and APA tissues, and the presence of 5-HT in APA tissues was studied by immunohistochemistry.


RESULTS
Real-time PCR analysis revealed that 5-HT4 receptor mRNA expression was 4.7-47 times higher in APA tissues than in normal glands. In situ hybridization studies showed that 5-HT4 receptor mRNAs were expressed in both zona glomerulosa and zona fasciculata/reticularis of the normal cortex and in groups of APA steroidogenic cells disseminated in the tumor tissues. Characterization of 5-HT4 receptor splice variants by RT-PCR revealed different profiles of expression in APAs versus normal adrenals. Isoforms (a) and (b) were not expressed in any APA but were present in the majority of normal adrenocortical tissues. Conversely, isoform (d) was expressed in 5/11 APAs but only in 1/7 adrenals. Immunohistochemical studies revealed the presence of 5-HT-immunoreactivity in both mast cells and clusters of steroidogenic cells in APA tissues.


CONCLUSIONS
Our results show overexpression and different splicing of the 5-HT4 receptor in APA tissues in comparison with normal adrenocortical tissue. They also demonstrate the presence of 5-HT in both mast cells and tumor steroidogenic cells, providing evidence for a possible autocrine/paracrine activation of aldosterone secretion within adenoma tissues.
Cartier
Dorthe
D
INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), Université de Rouen, 76821 Mont-Saint-Aignan, France.
Jégou
Sylvie
S
Parmentier
Françoise
F
Lihrmann
Isabelle
I
Louiset
Estelle
E
Kuhn
Jean-Marc
JM
Bastard
Christian
C
Plouin
Pierre-François
PF
Godin
Michel
M
Vaudry
Hubert
H
Lefebvre
Hervé
H
D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D007150:Immunohistochemistry; D020033:Protein Isoforms / Q000096:biosynthesis; D044422:Receptors, Serotonin, 5-HT4 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020033:Protein Isoforms; D044422:Receptors, Serotonin, 5-HT4; D000450:Aldosterone