Endocrine Abstracts (2002) 3 OC39

DHEA, a selective glucocorticoid receptor antagonist, studies in human lymphoblasts and hepatocytes

MS Sacco1,2, GV Valenti2, PCM Corvi Mora3, FCW Wu1 & DW Ray1


1Endocrine Sciences Research Group, Faculty of Medicine, Manchester, UK; 2Institute of Gerontology and Geriatrics, University of Parma, Italy; 3Euphar Group s.r.l Piacenza, Italy.


DHEA, the most abundant circulating adrenal steroid in humans has an uncertain role. DHEA declines with age, and has been suggested to antagonise some glucocorticoid actions. Previous studies have suggested that DHEA may have immunoregulatory, and metabolic functions. In rodent studies DHEA has been shown to improve insulin sensitivity, possibly by opposing glucocorticoid action. Glucocorticoids act on multiple tissues and employ a variety of mechanisms of action.

Aims: To analyse the impact of DHEA on glucocorticoid action using two in-vitro model systems: induction of lymphoblast apoptosis and hepatic gluconeogenic enzyme expression.

Human T lymphoblast cells (CEM C7A) were cultured in RPMI1640 with 10% fetal calf serum. Cells were incubated with 100nM dexamethasone to induce apoptosis. The high-affinity, type II glucocorticoid receptor antagonist, RU486, efficiently opposed induction of cell death at 1uM concentration. We tested progesterone, a naturally occurring glucocorticoid antagonist, in the same assay and again apoptosis was suppressed. We examined both native DHEA and the clathrate under the same conditions but there was no response.

The human hepatoma cell line, HepG2, was cultured in DMEM, plus 10% fetal calf serum , and 1% non-essential aminoacids. Cells were transfected by electroporation with a reporter gene derived from the human tyrosine aminotransferase gene glucocorticoid responsive region (TAT3-luc). The TAT reporter gene was induced by 100nM dexamethasone. This induction was efficiently repressed by co-incubation of the cells with 100nM native DHEA, and also 100nM RU486.

These data suggest that DHEA can inhibit the actions of glucocorticoids on glucoconeogenic enzyme induction, but we have not found any such an interaction between the steroids on lymphoblast apoptotic pathways.

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