To better understand the changes that occur following exposure to peroxisome proliferators. we utilized mRNA differential display and microarray to screen for peroxisome proliferator target genes apart from those involved in lipid metabolism in male C57B6 mice by using the ubiquitous plasticizer. di(2-ethylhexyl)phthalate (DEHP). One noted change was the dose-dependent suppression of the Mouse hormone metabolizing 3beta-hydroxysteroid dehydrogenase V (HSD3b5). which is specifically expressed in the male mouse liver. Northern analysis showed that HSD3b5 mRNA levels decreased dramatically upon one-day exposure to 2.0% dietary DEHP. and were nearly undetectable by one week of treatment. Food restriction also significantly suppressed HSD3b5 expression: however. in this case the suppression was delayed and to a lesser extent. Another mouse 3beta-hydroxysteroid dehydrogenase, HSD3b4, predominantly expressed in kidneys. was also regulated by DEHP and food restriction. The sex-specific gene, HSD3b5, was affected more by DEHP and food restriction than the tissue-specific gene. HSD3b4. (C) 2002 Elsevier Science (USA). All rights reserved.