Synergistic acceleration of thyroid hormone degradation by phenobarbital and the PPARα agonist WY14643 in rat hepatocytes

Wieneke, N.; Neuschäfer-Rube, Frank; Bode, Lars; Kuna, M; Andres, Janin; Carnevali, Luiz Carlos; Hirsch‐Ernst, Karen Ildico; Püschel, Gerhard

doi:10.1016/j.taap.2009.07.014

Cited by 13 publications

(7 citation statements)

References 43 publications

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“…Because PFOA is an agonist for PPARα, it is plausible that induction of hepatic UGT in PFAA-exposed rats (Yu et al 2009) could represent a PPARα-mediated response. The involvement of another PPARα agonist, WY 14643, in enhancing the hepatic degradation of thyroid hormone has recently been shown (Weineke et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Association between Serum Perfluorooctanoic Acid (PFOA) and Thyroid Disease in the U.S. National Health and Nutrition Examination Survey

Melzer

Rice

Depledge

et al. 2010

Environ Health Perspect

429

291

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BackgroundPerfluorooctanoic acid (PFOA, also known as C8) and perfluorooctane sulfonate (PFOS) are stable compounds with many industrial and consumer uses. Their persistence in the environment plus toxicity in animal models has raised concern over low-level chronic exposure effects on human health.ObjectivesWe estimated associations between serum PFOA and PFOS concentrations and thyroid disease prevalence in representative samples of the U.S. general population.MethodsAnalyses of PFOA/PFOS versus disease status in the National Health and Nutrition Examination Survey (NHANES) for 1999–2000, 2003–2004, and 2005–2006 included 3,974 adults with measured concentrations for perfluorinated chemicals. Regression models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and alcohol intake.ResultsThe NHANES-weighted prevalence of reporting any thyroid disease was 16.18% (n = 292) in women and 3.06% (n = 69) in men; prevalence of current thyroid disease with related medication was 9.89% (n = 163) in women and 1.88% (n = 46) in men. In fully adjusted logistic models, women with PFOA ≥ 5.7 ng/mL [fourth (highest) population quartile] were more likely to report current treated thyroid disease [odds ratio (OR) = 2.24; 95% confidence interval (CI), 1.38–3.65; p = 0.002] compared with PFOA ≤ 4.0 ng/mL (quartiles 1 and 2); we found a near significant similar trend in men (OR = 2.12; 95% CI, 0.93–4.82; p = 0.073). For PFOS, in men we found a similar association for those with PFOS ≥ 36.8 ng/mL (quartile 4) versus ≤ 25.5 ng/mL (quartiles 1 and 2: OR for treated disease = 2.68; 95% CI, 1.03–6.98; p = 0.043); in women this association was not significant.ConclusionsHigher concentrations of serum PFOA and PFOS are associated with current thyroid disease in the U.S. general adult population. More work is needed to establish the mechanisms involved and to exclude confounding and pharmacokinetic explanations.

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Section: Discussionmentioning

confidence: 99%

Association between Serum Perfluorooctanoic Acid (PFOA) and Thyroid Disease in the U.S. National Health and Nutrition Examination Survey

Melzer

Rice

Depledge

et al. 2010

Environ Health Perspect

429

291

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“…Therefore, the results of this study are considered to support that the thyroid gland response to DEHP exposure arises from CAR activation. Furthermore, thyroid effects via PPARα activation have been also reported as synergistic acceleration of thyroid hormone degradation related to PPARα-dependent CAR induction (Wieneke et al, 2009). However, rodents such as rat and mouse express PPARα mRNA at high levels in liver, whereas human PPARα mRNA is expressed at low levels in liver (Palmer et al, 1998;IARC, 2013).…”

Section: A B C D E Fmentioning

confidence: 99%

The effects on the endocrine system under hepatotoxicity induction by phenobarbital and di(2-ethylhexyl)phthalate in intact juvenile male rats

et al. 2019

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Phenobarbital (PB) and Di (2-ethylhexyl) phthalate (DEHP), an anti-epileptic drug and a plasticizer used in flexible polyvinylchloride formulations, respectively, are well-known typical hepatotoxicants. This study investigated the effects of PB (100 mg/kg/day) or DEHP (500 mg/kg/day) on the endocrine system in intact juvenile/peripubertal male rats exposed for 31 days beginning on postnatal day 23. Slight hormone level changes, histopathological changes in thyroid gland or induction of UDPglucuronosyltransferase in liver were observed in both the PB and DEHP groups. One of the assumed mechanisms inducing thyroid effects is predictable to be secondary changes based on the enhancement in thyroid hormone metabolism via the induction of hepatic microsomal enzymes. No reproductive systemrelated changes in organ weights, histopathology, and sexual maturation were observed in both groups. Lower testosterone level was observed in the PB group. CYP2B and CYP3A, which are involved in testosterone metabolism, were induced in liver of the PB group. There was no change of 17β-hydroxysteroid dehydrogenase activity in testis of both groups. Lower testosterone level in the PB-treated male rats was attributed to an indirect, hepatotoxicity-associated effect on the reproductive system and not to direct effects on testis such as the antiandrogenic activity and the inhibition of steroidogenesis. These results did not indicate that PB or DEHP exposure affects the endocrine system directly.

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“…18,19 Unless otherwise stated, hepatocytes were incubated for 330 min with ± 10 mM PGE 2 , stimulated with ± 10 nM insulin for the time indicated, washed with ice-cold PBS and snapfrozen. Hepatocytes were transfected immediately after plating with the plasmids indicated employing a modified calcium phosphate method described previously.…”

Section: Hepatocyte Cultivationmentioning

confidence: 99%

Stimulation of fat accumulation in hepatocytes by PGE2-dependent repression of hepatic lipolysis, β-oxidation and VLDL-synthesis

Henkel

Frede

Schanze

et al. 2012

Laboratory Investigation

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Hepatic steatosis is recognized as hepatic presentation of the metabolic syndrome. Hyperinsulinaemia, which shifts fatty acid oxidation to de novo lipogenesis and lipid storage in the liver, appears to be a principal elicitor particularly in the early stages of disease development. The impact of PGE 2 , which has previously been shown to attenuate insulin signaling and hence might reduce insulin-dependent lipid accumulation, on insulin-induced steatosis of hepatocytes was studied. The PGE 2 -generating capacity was enhanced in various obese mouse models by the induction of cyclooxygenase 2 and microsomal prostaglandin E-synthases (mPGES1, mPGES2). PGE 2 attenuated the insulin-dependent induction of SREBP-1c and its target genes glucokinase and fatty acid synthase. Nevertheless, PGE 2 enhanced incorporation of glucose into hepatic triglycerides synergistically with insulin. This was most likely due to a combination of a PGE 2 -dependent repression of (1) the key lipolytic enzyme adipose triglyceride lipase, (2) carnitine-palmitoyltransferase 1, a key regulator of mitochondrial b-oxidation, and (3) microsomal transfer protein, as well as (4) apolipoprotein B, key components of the VLDL synthesis. Repression of PGC1a, a common upstream regulator of these genes, was identified as a possible cause. In support of this hypothesis, overexpression of PGC1a completely blunted the PGE 2 -dependent fat accumulation. PGE 2 enhanced lipid accumulation synergistically with insulin, despite attenuating insulin signaling and might thus contribute to the development of hepatic steatosis. Induction of enzymes involved in PGE 2 synthesis in in vivo models of obesity imply a potential role of prostanoids in the development of NAFLD and NASH.

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Synergistic acceleration of thyroid hormone degradation by phenobarbital and the PPARα agonist WY14643 in rat hepatocytes

Cited by 13 publications

References 43 publications

Association between Serum Perfluorooctanoic Acid (PFOA) and Thyroid Disease in the U.S. National Health and Nutrition Examination Survey

Association between Serum Perfluorooctanoic Acid (PFOA) and Thyroid Disease in the U.S. National Health and Nutrition Examination Survey

The effects on the endocrine system under hepatotoxicity induction by phenobarbital and di(2-ethylhexyl)phthalate in intact juvenile male rats

Stimulation of fat accumulation in hepatocytes by PGE2-dependent repression of hepatic lipolysis, β-oxidation and VLDL-synthesis

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