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PGF2alpha Inhibits 20alpha-HSD Expression by Suppressing CK1alpha-induced ERK and SP1 Activation in the Corpus Luteum of Pregnant Mice

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Abstract

Prostaglandin F2α (PGF2α) is a luteolytic hormone that promotes parturition in mammals at the end of pregnancy by reducing progesterone secretion from the corpus luteum (CL). In rodents and primates, PGF2α rapidly converts progesterone to 20α-hydroxyprogesterone (20α-OHP) by promoting 20α-hydroxysteroid dehydrogenase (20α-HSD) expression. However, the specific mechanism of 20α-HSD regulation by PGF2α remains unclear. Casein Kinase 1α (CK1α) is a CK1 family member that regulates a variety of physiological functions, including reproductive development. Here, we investigated the effects of CK1α on pregnancy in female mice. Our experiments showed that CK1α is expressed in mouse CL, and its inhibition enhanced progesterone metabolism, decreased progesterone levels, and affected mouse embryo implantation. Further, CK1α mediated the effect of PGF2α on 20α-HSD in mouse luteal cells in vitro. Our results are the first to show that CK1α affects the 20α-HSD mRNA level by affecting the ERK signalling pathway to regulate the expression of the transcription factor SP1. These findings improve our understanding of PGF2α regulation of 20α-HSD.

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All data generated or analysed during the experiment are available upon request from the corresponding author.

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Acknowledgements

This work was supported by the Natural Science Foundation of China (32130098) and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China

    Qiao Gao & Sheng Cui

  2. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China

    Di Zhang, Jing-Lin Zhang, Bing-Jie Wang, Chen-Yang Lu & Sheng Cui

  3. Institute of Reproduction and Metabolism, Yangzhou University, Yangzhou, 225009, Jiangsu, China

    Di Zhang, Jing-Lin Zhang, Bing-Jie Wang, Chen-Yang Lu & Sheng Cui

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  1. Qiao Gao
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  2. Di Zhang
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Contributions

Qiao Gao, Di Zhang and Sheng Cui provided the experimental ideas and designed the experiments; Qiao Gao, Bing-Jie Wang and Chen-Yang Lu performed the experiments; Qiao Gao, Jing-Lin Zhang, Bing-Jie Wang and Chen-Yang Lu analysed the experimental data; Qiao Gao and Sheng Cui drafted the original manuscript.

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Correspondence to Sheng Cui.

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The animal experiments were approved by the Experimental Animal Welfare and Animal Experiment Ethics Review Committee of the China Agricultural University (Issue No. AW11402202-3–3).

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Gao, Q., Zhang, D., Zhang, JL. et al. PGF2alpha Inhibits 20alpha-HSD Expression by Suppressing CK1alpha-induced ERK and SP1 Activation in the Corpus Luteum of Pregnant Mice. Reprod. Sci. 31, 248–259 (2024). https://doi.org/10.1007/s43032-023-01322-9

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