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Cyclin-dependent kinase inhibitor 1B acts as a novel molecule to mediate testosterone synthesis and secretion in mouse Leydig cells by luteinizing hormone (LH) signaling pathway

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Abstract

Cyclin-dependent kinase inhibitor 1B (Cdkn1b, p27) plays important regulatory roles in many cellular processes. p27 is highly expressed in the mouse testis, but its roles and underlying mechanisms for testosterone synthesis and secretion remain not well understood. In the current study, we found that p27 located in Leydig cells and Sertoli cells of adult mouse testis. To explore the function of p27 in Leydig cells, p27 inhibitor and activator were injected into the adult mice, primary Leydig cells and TM3 cells. Our in vivo and in vitro results showed that change in the expression of p27 significantly alters the testosterone in both globe serum and culture medium. Meanwhile, the steroidogenesis-related gene expression was significantly regulated too. Moreover, our in vitro study showed that luteinizing hormone (LH) significantly increased p27 mRNA levels. Furthermore, our results proved that altering the mRNA expression of p27 leads to the synchronized changes of Lhcgr, Star, Cyp11a1, Hsd3b6, Cyp11a1, and Hsd17b3. Alterations of p27 also result in synchronously changes of RAF1 and ERK1/2 phosphorylation. These findings indicate that p27 plays vital roles in LH-induced testosterone production, providing a novel mechanism that p27 acts as an upstream molecule to elevate ERK1/2 phosphorylation to promote the expression of StAR and other cholesterol-metabolizing enzymes.

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Funding

This work was supported by the National Key Research and Developmental Program of China (2018YFC1003504), the Natural Science Foundation of China (31430083, 31772692), and the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Author notes

  1. Hongzhou Guo and Xuan Luo contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Agrobiotechnolpgy, College of Biological Sciences, China Agricultural University, Beijing, 10021, People’s Republic of China

    Hongzhou Guo, Xuan Luo, Longjie Sun & Sheng Cui

  2. Department of Reproductive Medicine and Genetics, The Seventh Medical Center of PLA General Hospital, Beijing, People’s Republic of China

    Jianhua Li

  3. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People’s Republic of China

    Sheng Cui

  4. Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, People’s Republic of China

    Sheng Cui

  5. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, People’s Republic of China

    Sheng Cui

  6. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, People’s Republic of China

    Sheng Cui

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  1. Hongzhou Guo
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Correspondence to Sheng Cui.

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Editor: Tetsuji Okamoto

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Guo, H., Luo, X., Sun, L. et al. Cyclin-dependent kinase inhibitor 1B acts as a novel molecule to mediate testosterone synthesis and secretion in mouse Leydig cells by luteinizing hormone (LH) signaling pathway. In Vitro Cell.Dev.Biol.-Animal 57, 742–752 (2021). https://doi.org/10.1007/s11626-021-00545-x

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  • DOI: https://doi.org/10.1007/s11626-021-00545-x

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