We have shown that 5-hydroxytryptamine (5-HT) receptor type 4 (5-HT4R) agonists stimulate aldosterone production in patients with aldosterone-producing adenoma (APA). Moreover, 5-HT-positive cells were observed in APA tissues and 5-HT4R mRNAs were markedly overexpressed in APAs in comparison with normal adrenals. All these results suggested that 5-HT produced by adrenal mast cells could be involved in the physiopathology of APAs. The aim of this work was to investigate the role of mast cells in the physiopathology of APA. Mast cells were characterized by specific immunohistochemical stainings using antibodies against tryptase. A high density of mast cells was observed in peritumoral adrenal tissue surrounding adenomas or in the tumor tissues. Tryptase labelling was also detected in some steroidogenic cells in the vicinity of mast cells, suggesting interactions between these two cell types. In addition, staining of APA tissues with antibodies anti-tryptophane hydroxylase, the key enzyme of 5-HT biosynthesis, revealed the presence of immunoreactivity in both mast cells and a subpopulation of steroidogenic cells. Interactions between mast cells and adrenocortical cells were explored using the LAD2 human mast cell line and the human adrenocortical cell line H295R. Administration of LAD2 cell culture supernatant to H295R cells induced a significant increase in aldosterone production which was potentiated when LAD2 cells were pre-incubated with the mast cell degranulator, compound 48/80. On the other hand, we observed that 5-HT stimulated H295R cells steroidogenesis via 5HT4R activation suggesting that the effect of mast cells supernatant could be at least in part due to 5-HT. These studies will be completed by co-cultures of mast cells and adrenocortical cells. Altogether, our results show that APA tissues contain numerous mast cells which may influence aldosterone secretion through local release of soluble regulatory factors.
Supported grants from the ANR (PHYSIO, ISPA), the FRHTA and the COMETE network (PHRC AOM 06179).
30 Apr - 04 May 2011
European Society of Endocrinology