Endocrine Abstracts (2002) 3 P202

Beta-adrenergic input exerts both acute and chronic effects on steroid production in H295R human adrenocortical cells

O Kosti, PJ King & JP Hinson

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

It is well established that catecholamines have potent actions on adrenocortical function and steroidogenesis in different species. The effect of these substances on steroid production of the human adrenal cell line H295R is the subject of this study. H295R is the first adrenocortical cell line capable of secreting the normal range of adrenal steroid products (i.e. mineralocorticoids, glucocorticoids and adrenal androgens) and since free of chromaffin cells, it appears to be a powerful tool to look at the direct effects of catecholamines on steroidogenesis, cell growth and differentiation. H295R cells were cultured in the presence of the synthetic catecholamine isoproterenol for 4 hours. Aldosterone, cortisol and DHEA production was measured using direct radioimmunoassays. Administration of 10-11-10-7 M isoproterenol produced a dose-dependent increase in secretion of aldosterone, cortisol and DHEA by H295R cells resulting in 3-fold, 2.5-fold and 2-fold stimulation respectively relative to basal. Analysis of mRNA from H295R cells together with studies using specific agonists suggest that this effect is mediated by the beta1 subclass of adrenergic receptor. Pre-treatment of H295R cells with isoproterenol significantly decreased the response of the cells to both AII and forskolin, two well established positive stimulants of this cell line. The mechanism of action of isoproterenol in altering adrenal responsiveness to stimulation in H295R remains to be elucidated.

These findings suggest that beta-adrenergic input is involved in steroid production of H295R cells and can alter adrenal responsiveness to stimulation.

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