Endocrine Abstracts

Bacterial Lipopolysaccharide directly stimulates Cortisol Secretion by Human Adrenal Cells

K. Vakharia, D Renshaw, J.P. Hinson

Department of Endocrinology, Division of General and Developmental Medicine, Barts and the London, Queen Mary School of Medicine and Dentistry, London, UK.

Adrenomedullin (ADM) is a potent vasorelaxant peptide recently identified in extracts of pheochromocytoma. Proadrenomedullin, a precursor of ADM, yields another vasodilatory peptide named proadrenomedullin N-terminal 20 peptide (PAMP). It has been established that ADM and PAMP are actively secreted in vascular smooth muscle and endothelial cells. Lipopolysaccharide (LPS), a bacterial product that potently induces septic shock, is a well known stimulant of ADM secretion in various cell types and is also known to stimulate activity of the hypothalamo-pituitary-adrenal axis.

In order to determine whether the actions of LPS may be dependent on local ADM and PAMP release, we carried out a series of experiments using different stimulants for 24 hours on the human adrenocortical cell line, H295R. We established that LPS (10ng/ml), like dibutyryl cAMP (1mM) and forskolin (10 micromolar) caused a significant increase in cortisol secretion (p<0.05, p<0.05, p<0.001, respectively). Aldosterone secretion was not altered by LPS stimulation. Furthermore, LPS had no effect on secretion of either ADM or PAMP by the H295R cells, although known stimulants, dibutyryl cAMP caused a significant increase in ADM secretion (p<0.01) and thyroid hormone (T3) (10 ^-8M) significantly increased ADM and PAMP secretion (p<0.001 and p<0.01, respectively) from control.

In conclusion, it appears that LPS is able to directly and selectively increase cortisol secretion in adrenal cells independent of the hypothalamo-pituitary-adrenal axis, without altering aldosterone release and in the absence of any change in ADM and PAMP secretion in response to endotoxin shock.

Supported by the British Heart Foundation.