ZBTB20 is required for anterior pituitary development and lactotrope specification

Dongmei Cao, Xianhua Ma, Jiao Cai, Jing Luan, An-Jun Liu, Rui Yang, Yi Cao, Xiaotong Zhu, Hai Zhang, Yu-Xia Chen, Yuguang Shi, Guang-Xia Shi, Dajin Zou, Xuetao Cao, Michael J. Grusby, Zhifang Xie () and Weiping J. Zhang ()
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Dongmei Cao: Second Military Medical University
Xianhua Ma: Second Military Medical University
Jiao Cai: Second Military Medical University
Jing Luan: Second Military Medical University
An-Jun Liu: Second Military Medical University
Rui Yang: Second Military Medical University
Yi Cao: Second Military Medical University
Xiaotong Zhu: Second Military Medical University
Hai Zhang: Second Military Medical University
Yu-Xia Chen: Second Military Medical University
Yuguang Shi: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio
Guang-Xia Shi: Dalian Medical University, 9 West Section
Dajin Zou: Changhai Hospital
Xuetao Cao: Chinese Academy of Medical Sciences
Michael J. Grusby: Harvard School of Public Health
Zhifang Xie: Second Military Medical University
Weiping J. Zhang: Second Military Medical University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11121

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