PHYSIOLOGICAL IMPORTANCE OF DEHYDROEPIANDROSTERONE

Dehydroepiandrosterone (DHEA), with its sulphate conjugate (DHEAS), is the most abundant steroid hormone in the circulation but its physiological importance is unclear. We propose that DHEA has either oestrogen-like or androgen-like effects depending on the hormonal milieu. In premenopausal women DHEA is either an oestrogen antagonist, perhaps through the competitive binding its metabolite of androstene-3 beta, 17 beta-diol (ADIOL) and oestradiol oestrogen receptor, or an androgen through its metabolism to androstenedione and testosterone. In women DHEA contributes to abdominal obesity and insulin resistance: in the premenopausal high oestrogen concentrations may counterbalance the androgenic effects of DHEA but in the postmenopausal metabolism to testosterone may increase the risk of cardiovascular disease, though this effect may be counterbalanced by the age-dependent decline in DHEA and also by the oestradiol-like effects of ADIOL. In some breast cancer cell lines in a low oestrogen milieu DHEA has an oestradiol-like effect, stimulating tumour growth, whereas in oestradiol abundance DHEA antagonises the growth-stimulating effect of oestradiol. In men, with an androgenic milieu, DHEA acts like an oestrogen and protects against cardiovascular disease.