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The effect of 17β-estradiol on the expression of dipeptidyl peptidase III and heme oxygenase 1 in liver of CBA/H mice



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.


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.


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.


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.


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.

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The authors would like to thank Iva Pešun Međimorec for her excellent technical contribution in performing surgical procedures of ovariectomy and Ana Jagust for her excellent technical assistance in performing immunohistochemical analyses. This research is funded by Croatian Ministry of Science, Education and Sports, Grant No. 098-0982464-1647, Grant No. 098-1191344-2938 and IBRO 2013 RHP.

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The authors declare no conflict of interest or any financial interest.

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Correspondence to S. Sobočanec.

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Mačak Šafranko, Ž., Sobočanec, S., Šarić, A. et al. The effect of 17β-estradiol on the expression of dipeptidyl peptidase III and heme oxygenase 1 in liver of CBA/H mice. J Endocrinol Invest 38, 471–479 (2015).

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  • Antioxidant enzyme
  • Gene and protein expression
  • Ovariectomy
  • Sex-related
  • Steroid hormone
  • Zinc peptidase
  • Immunohistochemistry