The Influence of Dihydrotestosterone on the Development of Graves' Disease in Female BALB/c Mice

Liu, Lianye; Wu, Liping; Gao, Anming; Zhang, Qi; Lv, Hongjun; Xu, Li; Xie, Chuanqing; Wu, Qian; Hou, Peng; Shi, Bingyin

doi:10.1089/thy.2015.0620

Cited by 18 publications

(17 citation statements)

References 41 publications

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“…38 Previous studies indicated that interstitial lymphocytic infiltration is not involved in the EAGD mouse model; thus, we asked whether the IL-4 was derived from draining lymph nodes. 39 Unexpectedly, IHC and flow cytometry (Figure 4d and data not shown) showed that IL-4, which activated p-STAT6, was not derived from lymphocytes but from TECs. We were initially surprised by the results.…”

Section: Discussionmentioning

confidence: 86%

“…39 Briefly, Ad-TSHR-289 and Ad-Con were propagated in HEK-293 cells, and the concentration of viral particles was determined by measuring the absorbance at 260 nm. The viruses used in the study were all stored in aliquots at −80 °C.…”

Section: Materials and Msethodsmentioning

confidence: 99%

“…Female mice aged 6–7 weeks were injected intramuscularly with Ad-TSHR289 or Ad-Con (5 × 10 10 particles in 50 μl of phosphate-buffered saline (PBS)) as described previously. 39 Mice were injected three times at 3-week intervals and were euthanized 4 weeks after the third injection to obtain blood and thyroid glands. The blood was collected and centrifuged at 1500 × g for 10 min, and the serum was stored at −80 °C until hormone analysis.…”

Section: Materials and Msethodsmentioning

confidence: 99%

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STAT6 deficiency ameliorates Graves’ disease severity by suppressing thyroid epithelial cell hyperplasia

et al. 2016

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Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD.

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Section: Discussionmentioning

confidence: 86%

Section: Materials and Msethodsmentioning

confidence: 99%

Section: Materials and Msethodsmentioning

confidence: 99%

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STAT6 deficiency ameliorates Graves’ disease severity by suppressing thyroid epithelial cell hyperplasia

et al. 2016

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“…Adenoviruses containing TSHR amino acid residues 1-289 (Ad-TSHR-289) and control adenovirus (Ad-Con) were constructed and purified as described. 39 Briefly, Ad-TSHR-289 and Ad-Con were propagated in HEK-293 cells, and the concentration of viral particles was determined by measuring the absorbance at 260 nm. The viruses used in the study were all stored in aliquots at − 80°C.…”

Section: Methodsmentioning

confidence: 99%

STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia

Zha¹

2017

EJEA

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“…Female mice infected with lymphcytic choriomeningitis virus (LCMV) and treated with DHT resulted in a decrease of LCMV-specific T cells and IFNγ production (Lin, et al 2010). In an induced mouse model of Grave’s disease (an autoimmune disease), mice that were treated with DHT before induction of Grave’s disease had significantly lower thyroid hormones compared to controls and significantly lower IFNγ and IL-2 production, suggesting that DHT had an immunosuppressive effect on CD4+ T H 1 T cells (Liu, et al 2016). …”

Section: Effects Of Androgen Deprivation On Immune Functionmentioning

confidence: 99%

Androgen deprivation and immunotherapy for the treatment of prostate cancer

Gamat¹,

McNeel²

2017

Endocrine-Related Cancer

112

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Prostate cancer is the most common newly diagnosed malignancy in men, and the second most common cause of cancer-related death in the United States. The primary treatment for recurrent prostate cancer is androgen deprivation, and this therapy is typically continued life-long for patients with metastatic prostate cancer. Androgens and androgen deprivation have profound effects on the immune system, a finding that has become more appreciated in an era where immune-based treatments for cancer are being increasingly explored. Preclinical studies suggest that androgen deprivation could potentially positively or negatively affect the use of approved immunotherapies, or those that are being developed for the treatment of prostate cancer. In this review, we provide a brief overview of the different types of androgen deprivation treatments used in the management of prostate cancer, discuss their effects on prostate tumors and the immune system, and how they are being explored in combination with immunotherapy. Finally, we address some of the critical questions in the field that must be answered to identify the best approaches to combine androgen deprivation with immunotherapy for the treatment of prostate cancer.

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The Influence of Dihydrotestosterone on the Development of Graves' Disease in Female BALB/c Mice

Abstract: DHT can alleviate the severity of GD by downregulating pro-autoimmune T helper 1 cells in female BALB/c mice. The protective influence was more noticeable with 5 mg and 15 mg doses of DHT.

Cited by 18 publications

References 41 publications

STAT6 deficiency ameliorates Graves’ disease severity by suppressing thyroid epithelial cell hyperplasia

STAT6 deficiency ameliorates Graves’ disease severity by suppressing thyroid epithelial cell hyperplasia

STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia

Androgen deprivation and immunotherapy for the treatment of prostate cancer

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