The role of testosterone in the regulation of P-glycoprotein functioning

Resumo

The functional activity of P-glycoprotein (Pgp) was studied in Chinchilla rabbits after orchiectomy and administration of testosterone undecanoate after surgery. The functional activity of Pgp was determined by the pharmacokinetics of fexofenadine, its marker substrate. In addition, the localization of the transport protein was assessed in the liver, kidney, and jejunum by the immunohistochemistry. It was found that a decrease in the serum testosterone concentration after orchiectomy leads to an increase in Pgp activity on the 14th and 21st days after the surgery, which is accompanied by an increase in the staining intensity of Pgp-positive epithelium membranes of the proximal and distal renal tubules. It was found that the administration of testosterone at a dose of 6 mg/kg body weight in the period after the surgery neutralizes these changes.