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J Pharmacol Exp Ther. 1992 Dec;263(3):1105-10.

Induction of peroxisomal enzyme activities by di-(2-ethylhexyl) phthalate in thyroidectomized rats with parathyroid replants.

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  • 1Division of Pharmacology, University of Missouri-Kansas City.


Previous studies suggest that thyroid hormones are involved in the mechanism of peroxisome proliferation. However, those studies utilized either surgically thyroidectomized animals, which are also parathyroidectomized, without calcium supplementation, or animals pretreated with antithyroid drugs, which are known to produce metabolic as well as morphometric changes in the liver. Therefore, these animal models confound conclusions drawn in previous studies. The purpose of the present study was to investigate the role of thyroid hormones in peroxisomal proliferation by the phthalate ester plasticizer, di-(2-ethylhexyl)phthalate (DEHP) in thyroidectomized rats with parathyroid replants. Using this model, it was found that DEHP-induced hepatomegaly was partially dependent on thyroid hormones. DEHP produced a thyromimetic effect, inducing the activity of malic enzyme and carnitine acetyltransferase in the absence of thyroid hormones. Additionally, DEHP-induced activities of catalase were shown to be dependent on thyroid hormones, whereas the thyroid status of the animal had no effect on DEHP-induced activities of the peroxisomal beta-oxidizing enzymes. These data further confirm that endocrine factors play variable roles in the process of induction of various peroxisomal enzymes caused by peroxisome proliferators.

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