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J Hypertens. 1997 Dec;15(12 Pt 2):1735-8.

Direct stimulation of cortisol secretion from the human NCI H295 adrenocortical cell line by vasoactive intestinal polypeptide.

Author information

1
Department of Clinical Biochemistry, University of Edinburgh, Scotland, UK.

Abstract

OBJECTIVE:

To investigate a possible direct action of vasoactive intestinal polypeptide (VIP) on adrenal cortisol secretion and to define its mechanism of action.

DESIGN:

The human adrenocortical carcinoma cell line NCI H295, which is not contaminated by medullary chromaffin cells, was used to aid distinction between a direct action of VIP on adrenocortical cells and an indirect mechanism involving VIP-stimulated release of catecholamines.

METHODS:

NCI H295 cells were challenged with 10(-11)-10(-7) mol/l VIP for 4 h, with or without prior exposure for 72 h to 10 micromol/l forskolin. Cortisol and cyclic AMP contents of the overlying media were measured using in-house radioimmunoassays. Cells were treated with 10(-8)-10(-6) mol/l adrenaline or 3.3 x 10(-8) mol/l VIP with and without 10(-8)-10(-6) mol/l propranolol to exclude the possibility that an indirect mechanism of action involving beta-adrenoceptors was operating.

RESULTS:

VIP treatment produced an increase in cortisol secretion without pre-incubation, but this was markedly enhanced by prior exposure of cells to forskolin. VIP was potent, with a threshold of 10(-11) mol/l (n = 4), reaching a maximum 3.9+/-0.9-fold increase in effect on cells pre-exposed to forskolin (n = 4) by 3.3 x 10(-8) mol/l. This increase matched the 4 h response to 10 micromol/l forskolin. Cortisol secretion was accompanied by a parallel, dose-dependent increase in accumulation of cAMP.

CONCLUSIONS:

VIP potently and directly stimulates secretion of cortisol from these adrenocortical cells of human origin via an adenylate cyclase-coupled VIP receptor. These findings raise the possibility of a significant and direct effect of VIP in the control of steroid secretion from the adrenal cortex in humans.

[Indexed for MEDLINE]

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