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垂体前叶发育和催乳素细胞分化需要ZBTB20。

ZBTB20 is required for anterior pituitary development and lactotrope specification.

作者信息

Cao Dongmei, Ma Xianhua, Cai Jiao, Luan Jing, Liu An-Jun, Yang Rui, Cao Yi, Zhu Xiaotong, Zhang Hai, Chen Yu-Xia, Shi Yuguang, Shi Guang-Xia, Zou Dajin, Cao Xuetao, Grusby Michael J, Xie Zhifang, Zhang Weiping J

机构信息

Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.

Department of Pathophysiology, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China.

出版信息

Nat Commun. 2016 Apr 15;7:11121. doi: 10.1038/ncomms11121.

DOI:10.1038/ncomms11121
PMID:27079169
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4835541/
Abstract

The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

摘要

腺垂体包含五种不同的激素产生细胞类型,它们的细胞分化是一个高度受调控且协调的过程。在此我们表明,ZBTB20对小鼠腺垂体发育和催乳素细胞特化至关重要。在腺垂体中,ZBTB20在所有成熟内分泌细胞类型中高表达,而在催乳素(PRL)产生细胞的前体——生长催乳素细胞中表达程度稍低。Zbtb20的缺失导致腺垂体发育不全、垂体性侏儒症以及成熟催乳素细胞完全缺失。在ZBTB20基因敲除小鼠中,尽管催乳素细胞系的定向分化通常已启动,但生长催乳素细胞在细胞系特化和扩增方面表现出严重缺陷。此外,内源性ZBTB20蛋白与Prl启动子结合,其敲低会降低催乳素细胞系MMQ中PRL的表达和分泌。另外,ZBTB20的过表达在体外增强了Prl启动子的转录活性。总之,我们的研究结果表明ZBTB20是腺垂体发育和催乳素细胞特化的关键调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/17e41b9c7812/ncomms11121-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/dd99a8790450/ncomms11121-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/95300e060a69/ncomms11121-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/02a690c0c507/ncomms11121-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/3f2c5e66c414/ncomms11121-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/2ae320371fc4/ncomms11121-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/64d61344704a/ncomms11121-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/8dc66a659852/ncomms11121-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/17e41b9c7812/ncomms11121-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/dd99a8790450/ncomms11121-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/95300e060a69/ncomms11121-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/02a690c0c507/ncomms11121-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/3f2c5e66c414/ncomms11121-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/2ae320371fc4/ncomms11121-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/64d61344704a/ncomms11121-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/8dc66a659852/ncomms11121-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcf/4835541/17e41b9c7812/ncomms11121-f8.jpg

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