Dihydrotestosterone regulates oxidative stress and immunosuppressive cytokines in a female BALB/c mouse model of Graves’ disease

Abstract

Background: Graves’ disease (GD) is an autoimmune disease that affects more women than men. In our previous study, a potent bioactive androgen, 5α-dihydrotestosterone (DHT) showed a protective effect against GD in female BALB/c mice. Evidence indicates that abnormal oxidative stress and immunosuppressive cytokines (TGF-β, IL-35) play critical roles in the pathogenesis and development of GD. The purpose of this research is to measure these cytokines and oxidative stress markers to explore potential protective mechanisms of DHT in a BALB/c mouse model of GD.

Methods: GD was induced in female BALB/c mice by intramuscular injection of an adenovirus expressing the A-subunit of the TSH receptor (Ad-TSHR289). DHT or a matching placebo was injected every 3 days. Mice were sacrificed four weeks after the third virus immunization to obtain blood, thyroid and spleen for further analysis.

Results: Thyroid hormones were significantly reduced in DHT treated GD mice. In addition, DHT attenuated thyroid oxidative injuries in GD mice, as shown by decreased total antioxidation capability (TAOC), superoxide dismutase (SOD) and the level of malondialdehyde (MDA). The levels of immunosuppressive cytokines (TGF-β, IL-35) in DHT group were significant higher compared with the GD group.

Conclusions: The results demonstrated that DHT could reduce the severity of GD in female BALB/c mice by regulating oxidative stress. The upregulation of immunosuppressive cytokines might be another important protective mechanism.

Keywords:

• Graves’ disease
• dihydrotestosterone
• mice
• oxidative stress
• Treg-Th17-related immunosuppressive cytokines

Acknowledgments

We would like to thank Dr. Basil Rapoport and Dr. Chunrong Chen (University of California, Los Angeles, CA) for providing us the plasmid expressing human TSHR289 (psv2-neo-ECE).

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Disclosure statement

No potential conflict of interest was reported by the authors.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the National Science Foundation of China (NSFC) [Grant No. 81471005 (B.S.), 81500690 (Y.W.)], Key Research and Development Project of Shaanxi Province [Grant No. 2017ZDXM-SF-060 (B.S.)], Natural Science Foundation of Shaanxi Province [2018JM70990 (Y.W.)], and the Fundamental Research Funds for the Central Universities [1191329875 (Y.W.)].