miR-375 acts as a novel factor modulating pituitary prolactin synthesis through Rasd1 and Esr1

in Journal of Endocrinology
Authors:
Jinglin Zhang College of Veterinary Medicine, su, Yangzhou University, Yangzhou, Jiang
Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, China

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Jie Gao State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China

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Di Zhang College of Veterinary Medicine, su, Yangzhou University, Yangzhou, Jiang

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Hui Liu College of Veterinary Medicine, su, Yangzhou University, Yangzhou, Jiang

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Kemian Gou College of Veterinary Medicine, su, Yangzhou University, Yangzhou, Jiang
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China

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, and
Sheng Cui College of Veterinary Medicine, su, Yangzhou University, Yangzhou, Jiang
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China

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Correspondence should be addressed to S Cui: cuisheng@cau.edu.cn

*(J Zhang, J Gao and D Zhang contributed equally to this work)

DOI:
https://doi.org/10.1530/JOE-20-0001
Volume/Issue:
Volume 250: Issue 1
Article Type:
Research Article
Page Range:
25–35
Online Publication Date:
28 Jun 2021
Copyright:
© Society for Endocrinology 2021
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Prolactin (PRL) is a pituitary hormone that regulates multiple physiological processes. However, the mechanisms of PRL synthesis have not been fully elucidated. The aims of the present study were to study the functions and the related mechanisms of miR-375 regulating PRL synthesis. We initially found that miR-375 mainly expressed in the lactotrophs of mouse pituitary gland. To identify the function of miR-375 in the pituitary gland, the miR-375 knockout mice were generated by using Crispr/Cas9 technique. The results showed that miR-375 knockout resulted in the decline of pituitary PRL mRNA and protein levels by 75.7 and 60.4%, respectively, and the serum PRL level reduced about 46.1%, but had no significant effect on FSH, LH and TSH. Further, we identified that Estrogen receptor 1 (alpha) (Esr1) was a downstream molecule of miR-375. The real-time PCR and Western blot results showed that ESR1 mRNA and protein levels markedly decreased by 40.9 and 42.9% in the miR-375 knockout mouse pituitary, and these were subsequently confirmed by the in vitro study using transfections of miR-375 mimics and inhibitors in pituitary lactotroph GH4 cells. Further, Rasd1 was predicted by bioinformatic tools and proved to be the direct target of miR-375 in lactotrophs using the dual-luciferase reporter assay. Rasd1-siRNA transfection results revealed the negative effect of Rasd1 in regulating ESR1. Collectively, the results presented here demonstrate that miR-375 positively modulates PRL synthesis through Rasd1 and Esr1, which are crucial for understanding the regulating mechanisms of pituitary hormone synthesis.

Supplementary Materials

    • Supplementary Figure 1
    • Supplementary Figure 2
    • Supplementary Figure 3
    • Supplementary Figure 4
    • Supplementary Table 1

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2021
Page(s):
11
Article Type:
Research Article
Received Date:
20 Apr 2021
Accepted Date:
20 May 2021
Print Publication Date:
01 Jul 2021
Online Publication Date:
28 Jun 2021
Keywords:
prolactin; miR-375; pituitary; lactotroph; ESR1

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