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High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway

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Summary

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1–7), but inhibited at later stage (days 7–14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.

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Authors and Affiliations

  1. Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, **an, 250021, China

    Tao Liu  (刘 涛), Yu-qian Cui  (崔玉倩), Han Zhao  (赵 涵), Hong-bin Liu  (刘洪彬), Shi-dou Zhao  (赵世斗), Yuan Gao  (高 媛), **ao-li Mu  (牟晓丽) & Zi-jiang Chen  (陈子江)

  2. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, **an, 250021, China

    Tao Liu  (刘 涛), Han Zhao  (赵 涵), Hong-bin Liu  (刘洪彬), Shi-dou Zhao  (赵世斗), Yuan Gao  (高 媛), **ao-li Mu  (牟晓丽) & Zi-jiang Chen  (陈子江)

  3. The Key Laboratory for Reproductive Endocrinology of Ministry of Education, **an, 250021, China

    Tao Liu  (刘 涛), Han Zhao  (赵 涵), Hong-bin Liu  (刘洪彬), Shi-dou Zhao  (赵世斗), Yuan Gao  (高 媛), **ao-li Mu  (牟晓丽) & Zi-jiang Chen  (陈子江)

  4. Shandong Provincial Key Laboratory of Reproductive Medicine, **an, 250021, China

    Tao Liu  (刘 涛), Han Zhao  (赵 涵), Hong-bin Liu  (刘洪彬), Shi-dou Zhao  (赵世斗), Yuan Gao  (高 媛), **ao-li Mu  (牟晓丽) & Zi-jiang Chen  (陈子江)

  5. Center for Reproductive Medicine, Tai’an Central Hospital, Tai’an, 271000, China

    Tao Liu  (刘 涛)

  6. Center for Reproductive Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Yu-qian Cui  (崔玉倩)

  7. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Bei**g, 100101, China

    Fei Gao  (高 飞)

Authors
  1. Tao Liu  (刘 涛)
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  2. Yu-qian Cui  (崔玉倩)
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  3. Han Zhao  (赵 涵)
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  5. Shi-dou Zhao  (赵世斗)
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  6. Yuan Gao  (高 媛)
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  7. **ao-li Mu  (牟晓丽)
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  8. Fei Gao  (高 飞)
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  9. Zi-jiang Chen  (陈子江)
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Corresponding authors

Correspondence to Fei Gao  (高 飞) or Zi-jiang Chen  (陈子江).

Additional information

These authors contributed equally to this work.

This project was supported by grants from the National Basic Research Program of China (973 program) (Nos. 2012CB944700 and 2011CB944502), the National Natural Science Foundation of China (No. 31371453), the Scientific Research Foundation of Shandong Province of Outstanding Young Scientist (No. 2012BSE27089), and 2012 Shandong Province Post-Doctoral Innovation Foundation (Nos. 201102017 and 201203052).

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Liu, T., Cui, Yq., Zhao, H. et al. High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 723–729 (2015). https://doi.org/10.1007/s11596-015-1497-z

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