New insights into the protective effects of DHEA1)

Abstract

AbstractNumerous studies investigated the effects of pharmacological doses of DHEA in animals. Among protective effects, antiglucocorticoid potencies, triggering and modulation of immunity and anticancerous effects were reported. Because DHEA levels decrease in aging humans, this steroid has been assayed as replacement therapy in elderly volunteers without striking evidence for beneficial effects. Examination of the investigations carried out in animals lead to suspect that, rather than DHEA, its metabolites produced in tissues could be responsible for some of the observed effects. Known as the “mother steroid”, DHEA is a precursor for androgenic and estrogenic steroid hormones. In addition, DHEA is hydroxylated at the 7α position by the cytochrome P450 7B1 (CYP7B1), and the 7α-hydroxy-DHEA produced is a substrate for the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which converts it into 7β-hydroxy-DHEA. Both 7-hydroxylated metabolites were shown to favor the onset of immunity in mice and the activation of memory T cells in humans. Other DHEA and testosterone-derived metabolites, namely epiandrosterone and 5α-androstane-3β,17β-diol, are also substrates for the CYP7B1 and their 7α-hydroxylated products were also converted into the 7β epimer by the 11β-HSD1. When assayed at doses 10