Bacterial lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells

Adrenomedullin and pro-adrenomedullin N-terminal 20 peptide (PAMP) are expressed in vascular cells and in the adrenal cortex and medulla. Lipopolysaccharide (LPS), a bacterial product that induces septic shock, is a potent stimulant of adrenomedullin secretion in vascular cell types and is also known to stimulate the hypothalamo-pituitary-adrenal axis (HPA). The present study was designed to investigate the actions of LPS on the human adrenocortical cell line, H295R. Exposure of cells to LPS for 24 hours had no effect on adrenomedullin or PAMP secretion, but was found to significantly and selectively increase cortisol secretion with no effect on aldosterone. Dibutyryl cAMP, however, caused a significant increase in both adrenomedullin and PAMP release over this time period. There are two conclusions which can be drawn from these observations. First that adrenomedullin and PAMP are regulated by different mechanisms in vascular and adrenal cells and second, that LPS is able to directly stimulate cortisol secretion, with implications for the physiological response to septic shock.