DHEA and DHEA sulfate differentially regulate neural androgen receptor and its transcriptional activity

Brain Research. Molecular Brain Research
Qianxing MoN G Simon

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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Citations

May 5, 2011·Cancer Biotherapy & Radiopharmaceuticals·Xu-Bao ShiRalph W deVere White
Sep 29, 2011·Neuroscience·M PesaresiR C Melcangi
May 12, 2009·The Journal of Steroid Biochemistry and Molecular Biology·Qianxing MoNeal G Simon
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Apr 4, 2006·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Agnieszka Basta-KaimWładysław Lasoń
Mar 10, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Qianxing MoNeal G Simon
Mar 6, 2009·Neuroreport·Carmen MéndezEnrique Pedernera
May 11, 2017·Journal of Neuroendocrinology·T-V Nguyen
Jan 29, 2011·Pharmacological Reports : PR·Bogusława BudziszewskaMarek Kaciński
Nov 4, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sik Yu So, Tor C Savidge

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