TY - JOUR T1 - Dehydroepiandrosterone Affects the Expression of Multiple Genes in Rat Liver Including 11β-Hydroxysteroid Dehydrogenase Type 1: A cDNA Array Analysis JF - Molecular Pharmacology JO - Mol Pharmacol SP - 722 LP - 731 DO - 10.1124/mol.63.3.722 VL - 63 IS - 3 AU - Shi Gu AU - Sharon L. Ripp AU - Russell A. Prough AU - Thomas E. Geoghegan Y1 - 2003/03/01 UR - http://molpharm.aspetjournals.org/content/63/3/722.abstract N2 - Dehydroepiandrosterone (DHEA) is a C-19 adrenal steroid precursor to the gonadal steroids. In humans, circulating levels of DHEA, as its sulfated conjugate, are high at puberty and throughout early adulthood but decline with age. Dietary supplementation to maintain high levels of DHEA purportedly has beneficial effects on cognitive memory, the immune system, and fat and carbohydrate metabolism. In rodents, DHEA is a peroxisome proliferator that induces genes for the classical peroxisomal and microsomal enzymes associated with this response. These effects are mediated through activation of peroxisome proliferator-activated receptor α (PPARα). However, DHEA can affect the expression of genes independently of PPARα, including the gene for the major inducible drug and xenobiotic metabolizing enzyme, cytochrome P450 3A23. To elucidate the biochemistry associated with DHEA treatment, we employed a cDNA gene expression array using liver RNA from rats treated with DHEA or the classic peroxisome proliferator nafenopin. Principal components analysis identified 30 to 35 genes whose expression was affected by DHEA and/or nafenopin. Some were genes previously identified as PPAR-responsive genes. Changes in expression of several affected genes were verified by quantitative reverse transcriptase-polymerase chain reaction. These included aquaporin 3, which was induced by DHEA and to a lesser extent nafenopin, nuclear tyrosine phosphatase, which was induced by both agents, and 11β-hydroxysteroid dehydrogenase 1, which was decreased by treatment with DHEA in a dose-dependent fashion. Regulation of 11β-hydroxysteroid dehydrogenase 1 expression is important since the enzyme is believed to amplify local glucocorticoid signaling, and its repression may cause some of the metabolic effects associated with DHEA. ER -