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Aldosterone from endometrial glands is benefit for human decidualization

Li, Shu Yun ; Song, Zhuo ; Yan, Ya Ping ; Li, Bo ; Song, Min Jie ; Liu, Yue Fang ; Yang, Zhen Shan LU orcid ; Li, Meng Yuan ; Liu, Ai Xia and Quan, Song , et al. (2020) In Cell Death and Disease 11(8).
Abstract

Local renin-angiotensin system (RAS) in female reproductive system is involved in many physiological and pathological processes, such as follicular development, ovarian angiogenesis, ovarian, and endometrial cancer progress. However, studies on the functional relevance of RAS in human endometrium are limited, especially for renin-angiotensin-aldosterone system (RAAS). In this study, we defined the location of RAS components in human endometrium. We found that angiotensin II type-1 receptor (AT1R) and aldosterone synthase (CYP11B2), major components of RAAS, are specifically expressed in endometrial gland during mid-secretory phase. Aldosterone receptor, mineralocorticoid receptor (MR), is elevated in stroma in mid-secretory... (More)

Local renin-angiotensin system (RAS) in female reproductive system is involved in many physiological and pathological processes, such as follicular development, ovarian angiogenesis, ovarian, and endometrial cancer progress. However, studies on the functional relevance of RAS in human endometrium are limited, especially for renin-angiotensin-aldosterone system (RAAS). In this study, we defined the location of RAS components in human endometrium. We found that angiotensin II type-1 receptor (AT1R) and aldosterone synthase (CYP11B2), major components of RAAS, are specifically expressed in endometrial gland during mid-secretory phase. Aldosterone receptor, mineralocorticoid receptor (MR), is elevated in stroma in mid-secretory endometrium. In vitro, MR is also activated by aldosterone during decidualization. Activated MR initiates LKB1 expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. The impact of PDK4 on decidualization is independent on PDHE1α inactivation. Based on co-immunoprecipitation, PDK4 interacts with p-CREB to prevent its ubiquitination for facilitating decidualization via FOXO1. Restrain of MR activation interrupts LKB1/p-AMPK/PDK4/p-CREB/FOXO1 pathway induced by aldosterone, indicating that aldosterone action on decidualization is mainly dependent on MR stimulation. Aldosterone biosynthesized in endometrial gland during mid-secretory phase promotes decidualization via activating MR/LKB1/p-AMPK/PDK4/p-CREB/FOXO1 signaling pathway. This study provides the valuable information for understanding the underlying mechanism during decidualization.

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publishing date
type
Contribution to journal
publication status
published
in
Cell Death and Disease
volume
11
issue
8
article number
679
publisher
Nature Publishing Group
external identifiers
  • pmid:32826848
  • scopus:85089658389
ISSN
2041-4889
DOI
10.1038/s41419-020-02844-9
language
English
LU publication?
no
additional info
Funding Information: This work was supported by National Key Research and Development Program of China [2018YFC1004403] and National Natural Science Foundation of China [31871511 and 31671563]. Publisher Copyright: © 2020, The Author(s).
id
5ee8f2ec-590f-47cc-8c34-62ed2ed8aad2
date added to LUP
2024-02-28 14:58:32
date last changed
2024-03-30 09:33:22
@article{5ee8f2ec-590f-47cc-8c34-62ed2ed8aad2,
  abstract     = {{<p>Local renin-angiotensin system (RAS) in female reproductive system is involved in many physiological and pathological processes, such as follicular development, ovarian angiogenesis, ovarian, and endometrial cancer progress. However, studies on the functional relevance of RAS in human endometrium are limited, especially for renin-angiotensin-aldosterone system (RAAS). In this study, we defined the location of RAS components in human endometrium. We found that angiotensin II type-1 receptor (AT<sub>1</sub>R) and aldosterone synthase (CYP11B2), major components of RAAS, are specifically expressed in endometrial gland during mid-secretory phase. Aldosterone receptor, mineralocorticoid receptor (MR), is elevated in stroma in mid-secretory endometrium. In vitro, MR is also activated by aldosterone during decidualization. Activated MR initiates LKB1 expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. The impact of PDK4 on decidualization is independent on PDHE1α inactivation. Based on co-immunoprecipitation, PDK4 interacts with p-CREB to prevent its ubiquitination for facilitating decidualization via FOXO1. Restrain of MR activation interrupts LKB1/p-AMPK/PDK4/p-CREB/FOXO1 pathway induced by aldosterone, indicating that aldosterone action on decidualization is mainly dependent on MR stimulation. Aldosterone biosynthesized in endometrial gland during mid-secretory phase promotes decidualization via activating MR/LKB1/p-AMPK/PDK4/p-CREB/FOXO1 signaling pathway. This study provides the valuable information for understanding the underlying mechanism during decidualization.</p>}},
  author       = {{Li, Shu Yun and Song, Zhuo and Yan, Ya Ping and Li, Bo and Song, Min Jie and Liu, Yue Fang and Yang, Zhen Shan and Li, Meng Yuan and Liu, Ai Xia and Quan, Song and Yang, Zeng Ming}},
  issn         = {{2041-4889}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Cell Death and Disease}},
  title        = {{Aldosterone from endometrial glands is benefit for human decidualization}},
  url          = {{http://dx.doi.org/10.1038/s41419-020-02844-9}},
  doi          = {{10.1038/s41419-020-02844-9}},
  volume       = {{11}},
  year         = {{2020}},
}