Dehydroepiandrosterone sulphate is a steroid product of the adrenal gland, which circulates in micromolar concentrations, but whose function is unclear. Epidemiological studies have suggested that high circulating DHEAS levels may be protective against cardiovascular disease. The present study was designed to determine whether DHEAS altered vascular cell growth using the human microvascular endothelial cell line HMEC.
HMECs were grown in MCDB131 medium containing 5%FBS, 10ng/ml EGF, 20mM L-glutamine and 1% penicillin/streptomycin. Cells were plated at a density of 250,000 per well in 6-well plates. Cells were serum-starved for 24 hours and the media was then replaced with full serum-containing media in the presence or absence of DHEAS or other steroids. Cells were harvested at 0, 24, 48 and 72 hours and counted with a haemocytometer, using trypan blue exclusion.
Over a 72hour period the number of cells present increased by approximately 3-fold. DHEA and DHEAS both caused a highly significant and dose-dependent decrease in the number of cells present at the end of the incubation period. The minimum effective concentration of DHEA was 1umol/l, DHEAS was 10nmol/l. Other steroids (oestradiol, dihydrotestosterone and cortisol) had no effect at concentrations up to 10umol/l.
These data suggest that DHEAS, at physiological concentrations, inhibits the proliferation of vascular endothelial cells. The effect is clearly not mediated by activation of oestrogen, androgen or glucocorticoid receptors. The mechanism of this effect is presently under investigation.
22 - 24 Mar 2004
British Endocrine Societies