DHEA and DHEA sulfate differentially regulate neural androgen receptor and its transcriptional activity.
Brain Res Mol Brain Res
; 126(2): 165-72, 2004 Jul 26.
Article
en En
| MEDLINE
| ID: mdl-15249140
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 promoted AR-mediated reporter gene expression as a function of dose and the effect was comparable with or without the addition of TRIL. In contrast, DHEA-S treatment failed to increase AR level in the mouse brain or GT1-7 cells and modestly induced AR-mediated reporter gene expression only at substantially elevated concentrations compared to DHEA. The findings demonstrate that DHEA is capable of exerting androgenic effects through AR while the androgenicity of DHEA-S is negligible. The implications of the results for models of the mechanism of action of DHEA and its sulfate ester, DHEA-S, in the brain are considered.
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Bases de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Receptores Androgénicos
/
Adipatos
/
Sulfato de Deshidroepiandrosterona
/
Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Brain Res Mol Brain Res
Asunto de la revista:
BIOLOGIA MOLECULAR
/
CEREBRO
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos