Received for publication March 21, 2005.
Revised July 30, 2005.
Accepted for publication August 3, 2005.

Modulation of P-glycoprotein expression in hyperthyroid rat tissues

Abstract

P-glycoprotein (Pgp) is expressed in various normal tissues and plays an important role in drug absorption and disposition. In addition, it is supposed that alterations in the expression levels of Pgp are involved in the inter- and intraindividual variability of pharmacokinetics of many drugs. Since pharmacokinetic properties of various drugs are altered in patients with thyroid disorders, we examined the expression of Pgp and mdr1a/1b mRNA in the kidney, liver, jejunum and ileum from euthyroid and hyperthyroid rats. Western blot analysis revealed that Pgp expression was markedly increased in the kidney and liver of hyperthyroid rats. In contrast, it was slightly increased in the jejunum and ileum. Mdr1a/1b mRNA levels were significantly increased in the kidney of hyperthyroid rats. However, those were not increased in the liver as well as in the jejunum and ileum of hyperthyroid rats. Expression levels of bile salt export pump and mdr2 mRNA were also unchanged in hyperthyroid rat liver. Taken together, these findings suggest that thyroid hormone induces Pgp expression in a tissue-selective manner and the modulation of mdr1a/1b mRNA expression in the hyperthyroid state varied among tissues.

Key words: drug disposition, hormonal regulation, p-glycoprotein

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