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J Steroid Biochem Mol Biol. 2013 Jan;133:93-100. doi: 10.1016/j.jsbmb.2012.09.014. Epub 2012 Sep 20.

Effects of nuclear receptor transactivation on steroid hormone synthesis and gene expression in porcine Leydig cells.

Author information

1
Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada N1G2W1.

Abstract

Male pigs are routinely castrated at a young age to prevent the formation of androstenone, a 16-androstene testicular steroid that is a major component of boar taint. The practice of castration has been increasingly viewed as unfavorable, due to both economic considerations and animal welfare concerns. Other means of controlling boar taint, including reducing the synthesis of androstenone in the testes, would eliminate the need for castration. In this study, we determined the effects of transactivation of three nuclear receptors, the constitutive androstane receptor (CAR), pregnane X receptor (PXR), and farnesoid X receptor (FXR), on gene expression and steroid hormone metabolism in primary porcine Leydig cells. Primary cells were isolated from mature boars, and transcript expression levels were assayed using real-time PCR. The transcripts of interest included porcine orthologs of common phase I and phase II metabolic enzymes, enzymes involved in steroidogenesis, and transcripts previously shown to be differentially expressed in boars with high androstenone and boar taint levels. Transactivation of CAR, PXR, or FXR increased the expression of several genes involved in steroidogenesis, including cytochrome B5A (CYB5A) and cytochrome B5 reductase 1 (CYB5R1), as well as hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4) and retinol dehydrogenase 12 (RDH12). Treatment with (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO), a CAR agonist, or rifampicin (RIF), a PXR agonist, resulted in significantly (p<0.05) decreased sex steroid production and significantly (p<0.05) increased production of 16-androstene steroids. Treatment with the FXR agonist chenodeoxycholic acid (CDCA) resulted in significantly (p<0.05) decreased sex steroid production. These results indicate that transactivation of these nuclear receptors may lead to increased levels of 16-androstene steroids, likely by altering the activity of CYP17A1 through CYB5A and CYB5R1 to the andien-β synthase reaction and away from the 17α-hydroxylase and C17, 20 lyase reactions.

PMID:
23000191
DOI:
10.1016/j.jsbmb.2012.09.014
[Indexed for MEDLINE]

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