Regulation of phase I and phase II steroid metabolism enzymes by PPAR alpha activators

Toxicology
Li-Qun FanJ Christopher Corton

Abstract

Peroxisome proliferators (PP) are a large class of structurally diverse chemicals that mediate their effects in the liver mainly through the peroxisome proliferator-activated receptor alpha (PPARalpha). Exposure to some PP results in alterations of steroid levels that may be mechanistically linked to adverse effects in reproductive organs. We hypothesized that changes in steroid levels after PP exposure are due to alterations in the levels of P450 enzymes that hydroxylate testosterone and estrogen. In testosterone hydroxylase assays, exposure to the PP, WY-14,643 (WY), gemfibrozil or di-n-butyl phthalate (DBP) led to compound-specific increases in 6beta and 16beta-testosterone and androstenedione hydroxylase activities and decreases in 16alpha, 2alpha-hydroxylase activities by all three PP. The decreases in 16alpha and 2alpha-testosterone hydroxylase activity can be attributed to a 2alpha and 16alpha- testosterone hydroxylase, CYP2C11, which we previously showed was dramatically down-regulated in these same tissues (Corton et al., 1998; Mol. Pharmacol. 54, 463-473). To explain the increases in 6beta- and 16beta-testosterone hydroxylase activities, we examined the expression of P450 family members known to carry out these functi...Continue Reading

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Citations

Jul 6, 2013·Environmental Science and Pollution Research International·Angeliki LyssimachouCinta Porte
Sep 13, 2006·Environmental Health Perspectives·Nagalakshmi Keshava, Jane C Caldwell
Jun 17, 2009·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Jörg OehlmannCharles R Tyler
Aug 15, 2009·PPAR Research·Melissa Runge-Morris, Thomas A Kocarek
Jan 22, 2013·Drug Metabolism Reviews·Melissa Runge-MorrisCharles N Falany
Dec 27, 2011·Mutation Research·Ivan Rusyn, J Christopher Corton
Dec 7, 2010·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Akira KubotaHisato Iwata
Oct 22, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·J Christopher Corton, Paula J Lapinskas
May 10, 2008·Toxicologic Pathology·Mitchell B RosenChristopher Lau
Nov 13, 2007·The Journal of Pharmacology and Experimental Therapeutics·Yazen Alnouti, Curtis D Klaassen
Aug 19, 2017·PPAR Research·Qiansheng Huang, Qionghua Chen
Dec 2, 2020·Current Drug Metabolism·Sangita Maiti DuttaSmarajit Maiti

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