Background: 17β-estradiol (E₂) has well-established cardioprotective, antioxidant and neuroprotective role, and exerts a vast range of biological effects in both sexes. Dipeptidyl peptidase III (DPP III) is protease involved as activator in Keap1-Nrf2 signalling pathway, which is important in cellular defense to oxidative and electrophilic stress. It is generally accepted that oxidative stress is crucial in promoting liver diseases.
Objective: To examine the effect of E₂ on the expression of DPP III and haeme oxygenase 1 (HO-1) in liver of adult CBA/H mice of both sexes.
Methods: Gene and protein expressions of studied enzymes were determined by quantitative real-time PCR and Western blot analysis. Immunohistochemistry was performed to analyse the localization of both proteins in different liver cell types.
Results: Ovariectomy diminished expression of DPP III and HO-1 proteins. E₂ administration abolished this effect, and even increased these proteins above the control. A significant enhancement in DPP III protein was found in E₂-treated males, as well. A decrease in the expression of HO-1, but not of the DPP III gene, was detected in the liver of ovariectomized females. HO-1 protein was found localized in the pericentral areas of hepatic lobules (Kupffer cells and hepatocytes), whilst DPP III showed a uniform distribution within hepatic tissue.
Conclusions: We demonstrate for the first time that E₂ influences the protein level of DPP III in vivo, and confirm earlier finding on HO-1 gene upregulation by 17β-estradiol. These results additionally confer new insights into complexity of protective action of E₂.
Keywords: Antioxidant enzyme; Gene and protein expression; Immunohistochemistry; Ovariectomy; Sex-related; Steroid hormone; Zinc peptidase.