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. 2021 Sep;236(9):6706-6725.
doi: 10.1002/jcp.30334. Epub 2021 Feb 17.

Circadian clock gene BMAL1 controls testosterone production by regulating steroidogenesis-related gene transcription in goat Leydig cells

Yaoyao Xiao  1   2 , Lijia Zhao  1   2 , Weidong Li  3 , Xiaoyu Wang  1   2 , Tiantian Ma  1   2 , Luda Yang  1   2 , Lei Gao  1   2 , Cuimei Li  1   2 , Manhui Zhang  1   2 , Dan Yang  1   2 , Jing Zhang  1   2 , Haizhen Jiang  1   2 , Hongcong Zhao  1   2 , Yiqun Wang  1   2 , Hsu-Wen Chao  4   5 , Aihua Wang  2   6 , Yaping Jin  1   2 , Huatao Chen  1   2
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Circadian clock gene BMAL1 controls testosterone production by regulating steroidogenesis-related gene transcription in goat Leydig cells

Yaoyao Xiao et al. J Cell Physiol. 2021 Sep.

Abstract

Testosterone is produced by Leydig cells (LCs) and undergoes diurnal changes in serum levels in rats, mice, and humans, but little is known in goats. The present study revealed that goat serum testosterone levels displayed diurnal rhythmic changes (peak time at ZT11.2). Immunohistochemical staining showed that BMAL1, a circadian clock protein, is highly expressed in goat LCs. ELISA revealed that both hCG (0-5 IU/ml) and 22R-OH-cholesterol (0-30 μM) addition stimulated testosterone synthesis in primary goat LCs in a dose-dependent manner. Treating goat LCs with hCG (5 IU/ml) significantly increased intracellular cAMP levels. Additionally, real-time quantitative polymerase chain reaction (PCR) analysis revealed that the circadian clock (BMAL1, PER1, PER2, DBP, and NR1D1) and steroidogenesis-related genes (SF1, NUR77, StAR, HSD3B2, CYP17A1, CYP11A1, and HSD17B3) showed rhythmic expression patterns in goat LCs following dexamethasone synchronization. Several Bmal1-Luc circadian oscillations were clearly observed in dexamethasone-treated goat LCs transfected with the pLV6-Bmal1-Luc plasmid. BMAL1 knockdown significantly downregulated mRNA levels of PER2, NR1D1, DBP, StAR, HSD3B2, SF1, NUR77, and GATA4, and dramatically decreased StAR and HSD3B2 protein levels and testosterone production. In contrast, BMAL1 overexpression significantly increased the mRNA and protein expression levels of StAR and HSD17B3 and enhanced testosterone production. Reporter assays revealed that goat BMAL1, or in combination with mouse CLOCK, activated goat HSD17B3 transcription in vitro. These data indicate that BMAL1 contributes to testosterone production by regulating transcription of steroidogenesis-related genes in goat LCs, providing a basis for further exploring the underlying mechanism by which the circadian clock regulates ruminant reproductive capability.

Keywords: BMAL1; HSD17B3; Leydig cells; StAR; goat; testosterone.

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References

REFERENCES

    1. Ahmad, N. , & Noakes, D. E. (1995). Seasonal-variations in testis size, libido and plasma testosterone concentrations in British goats. Animal Science, 61(3), 553-559. https://doi.org/10.1017/S1357729800014132
    1. Alvarez, J. D. , Chen, D. C. , Storer, E. , & Sehgal, A. (2003). Non-cyclic and developmental stage-specific expression of circadian clock proteins during murine spermatogenesis. Biology of Reproduction, 69(1), 81-91. https://doi.org/10.1095/biolreprod.102.011833
    1. Alvarez, J. D. , Hansen, A. , Ord, T. , Bebas, P. , Chappell, P. E. , Giebultowicz, J. M. , Williams, C. , Moss, S. , & Sehgal, A. (2008). The circadian clock protein BMAL1 is necessary for fertility and proper testosterone production in mice. Journal of Biological Rhythms, 23(1), 26-36. https://doi.org/10.1177/0748730407311254
    1. Alvarez, J. D. , & Sehgal, A. (2005). The thymus is similar to the testis in its pattern of circadian clock gene expression. Journal of Biological Rhythms, 20(2), 111-121. https://doi.org/10.1177/0748730404274078
    1. An, S. Y. , Zhang, G. M. , Liu, Z. F. , Zhou, C. , Yang, P. C. , & Wang, F. (2019). MiR-1197-3p regulates testosterone secretion in goat Leydig cells via targeting PPARGC1A. Gene, 710, 131-139. https://doi.org/10.1016/j.gene.2019.05.057

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