Lipopolysaccharide directly stimulates aldosterone production via toll-like receptor 2 and toll-like receptor 4 related PI3K/Akt pathway in rat adrenal zona glomerulosa cells

The level of circulating endotoxin is related to the severity of cardiovascular disease. One of the indexes for the prognosis of cardiovascular disease is the plasma aldosterone level. Recently, the Toll‐like receptors (TLRs), lipopolysaccharide (LPS)‐regulated receptors, were found not only to mediate the inflammatory response but also to be important in the adrenal stress response. Whether LPS via TLRs induced aldosterone production in adrenal zona glomerulosa (ZG) cells was not clear. Our results suggest that LPS‐induced aldosterone secretion in a time‐ and dose‐dependent manner and via TLR2 and TLR4 signaling pathway. Administration of LPS can enhance steroidogenesis enzyme expression such as scavenger receptor‐B1 (SR‐B1), steroidogenic acute regulatory protein (StAR) and P450 side chain cleavage (P450scc) enzyme. LPS‐induced SR‐B1 and StAR protein expression are abolished by TLR2 blocker. Furthermore, we demonstrated that phosphorylation of Akt was elevated by LPS treatment and reduced by TLR2 blockers, TLR4 blockers, and LY294002 (PI3K inhibitor). Those inhibitors of PI3K/Akt pathways also abolish LPS‐induced aldosterone secretion and SR‐B1 protein level. In conclusion, LPS‐induced aldosterone production and SR‐B1 proteins expression are through the TLR2 and TLR4 related PI3K/Akt pathways in adrenal ZG cells. J. Cell. Biochem. 111: 872–880, 2010. © 2010 Wiley‐Liss, Inc.