Natural Product-Induced Modulation of Androstenone Metabolism in Porcine Hepatocytes
The nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and farnesoid X receptor (FXR) regulate the hepatic metabolism of androstenone, a testicular steroid that accumulates in the fat of intact male pigs and causes boar taint. This study evaluated natural product-de...
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2025-07-01
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| author | Christine Bone E. James Squires |
| author_facet | Christine Bone E. James Squires |
| author_sort | Christine Bone |
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| description | The nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and farnesoid X receptor (FXR) regulate the hepatic metabolism of androstenone, a testicular steroid that accumulates in the fat of intact male pigs and causes boar taint. This study evaluated natural product-derived compounds and conventional agonists targeting these nuclear receptors for their effects on androstenone metabolism in primary hepatocytes from slaughter-weight boars, to assess their potential as treatments for boar taint. Cells were incubated with natural products, conventional agonists, or dimethyl sulfoxide (DMSO; control), then being treated with androstenone. Culture media and cells were analyzed to assess changes in androstenone metabolism and gene expression. <i>UGT1A6</i> was upregulated by treatments targeting both PXR and CAR and downregulated by FXR agonists. Additionally, <i>PGC1α</i> and <i>NR2F1</i> were downregulated by compounds targeting PXR/CAR, while <i>FXR</i> and <i>NR0B2</i> were upregulated and <i>HNF4α</i> downregulated by treatments acting on FXR. The natural products diallyl sulfide (DAS) and (Z)-guggulsterone (GUG) increased overall androstenone metabolism (DAS, GUG) and the production of Phase I androstenol metabolites (DAS), but only in hepatocyte culture replicates that responded positively to these treatments. Although gene expression was similar between positive-response and negative/non-responsive replicates following treatments, negative/non-responsive replicates for several treatments had higher basal expression of <i>UGT2B31</i>, <i>UGT2A1</i>, and <i>SIRT1</i> and lower basal expression of <i>FXR</i>, <i>PXR</i>, and <i>NR0B1</i> compared to positive-response replicates. These findings suggest that DAS and GUG may be promising treatments for boar taint, specifically in animals with lower basal rates of androstenone metabolism and higher expression of key nuclear receptors. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-66cc4f77bba14d24b401a3741e5ea3cb2025-08-20T03:35:57ZengMDPI AGAnimals2076-26152025-07-011515219910.3390/ani15152199Natural Product-Induced Modulation of Androstenone Metabolism in Porcine HepatocytesChristine Bone0E. James Squires1Department of Animal Biosciences, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Animal Biosciences, University of Guelph, Guelph, ON N1G 2W1, CanadaThe nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and farnesoid X receptor (FXR) regulate the hepatic metabolism of androstenone, a testicular steroid that accumulates in the fat of intact male pigs and causes boar taint. This study evaluated natural product-derived compounds and conventional agonists targeting these nuclear receptors for their effects on androstenone metabolism in primary hepatocytes from slaughter-weight boars, to assess their potential as treatments for boar taint. Cells were incubated with natural products, conventional agonists, or dimethyl sulfoxide (DMSO; control), then being treated with androstenone. Culture media and cells were analyzed to assess changes in androstenone metabolism and gene expression. <i>UGT1A6</i> was upregulated by treatments targeting both PXR and CAR and downregulated by FXR agonists. Additionally, <i>PGC1α</i> and <i>NR2F1</i> were downregulated by compounds targeting PXR/CAR, while <i>FXR</i> and <i>NR0B2</i> were upregulated and <i>HNF4α</i> downregulated by treatments acting on FXR. The natural products diallyl sulfide (DAS) and (Z)-guggulsterone (GUG) increased overall androstenone metabolism (DAS, GUG) and the production of Phase I androstenol metabolites (DAS), but only in hepatocyte culture replicates that responded positively to these treatments. Although gene expression was similar between positive-response and negative/non-responsive replicates following treatments, negative/non-responsive replicates for several treatments had higher basal expression of <i>UGT2B31</i>, <i>UGT2A1</i>, and <i>SIRT1</i> and lower basal expression of <i>FXR</i>, <i>PXR</i>, and <i>NR0B1</i> compared to positive-response replicates. These findings suggest that DAS and GUG may be promising treatments for boar taint, specifically in animals with lower basal rates of androstenone metabolism and higher expression of key nuclear receptors.https://www.mdpi.com/2076-2615/15/15/2199boar taintandrostenonenatural productsmetabolismPXRCAR |
| spellingShingle | Christine Bone E. James Squires Natural Product-Induced Modulation of Androstenone Metabolism in Porcine Hepatocytes Animals boar taint androstenone natural products metabolism PXR CAR |
| title | Natural Product-Induced Modulation of Androstenone Metabolism in Porcine Hepatocytes |
| title_full | Natural Product-Induced Modulation of Androstenone Metabolism in Porcine Hepatocytes |
| title_fullStr | Natural Product-Induced Modulation of Androstenone Metabolism in Porcine Hepatocytes |
| title_full_unstemmed | Natural Product-Induced Modulation of Androstenone Metabolism in Porcine Hepatocytes |
| title_short | Natural Product-Induced Modulation of Androstenone Metabolism in Porcine Hepatocytes |
| title_sort | natural product induced modulation of androstenone metabolism in porcine hepatocytes |
| topic | boar taint androstenone natural products metabolism PXR CAR |
| url | https://www.mdpi.com/2076-2615/15/15/2199 |
| work_keys_str_mv | AT christinebone naturalproductinducedmodulationofandrostenonemetabolisminporcinehepatocytes AT ejamessquires naturalproductinducedmodulationofandrostenonemetabolisminporcinehepatocytes |