Abstract
The mechanism of action of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S), two interconvertable neurosteroids, has not been fully characterized in the central nervous system (CNS). Previous studies demonstrated that DHEA was intrinsically androgenic, suggesting that it may act through a genomic pathway. However, it is not known whether DHEA-S also produces androgenic effects, an important question given that the concentration of DHEA-S in brain is some 7-12 times that of DHEA. The current study compared the potential androgenic effects of DHEA-S with DHEA by examining their capacity to induce two characteristic effects of an androgenic compound. These included the ability to (1) up-regulate neural androgen receptor (AR) protein level in mouse brain and immortalized GT1-7 hypothalamic cells and (2) assess their effect on reporter gene expression through AR in CV-1 cells cotransfected with pSG5-AR and pMMTV-ARE-CAT reporter. Semi-quantitative Western blot analysis showed that DHEA treatment significantly augmented AR in mouse brain and GT1-7 cells in a dose-dependent manner and that these effects were not blocked by trilostane (TRIL), a known 3beta-hydroxysteroid dehydrogenase inhibitor. DHEA also promo...Continue Reading
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