title: ZBTB20 is required for anterior pituitary development and lactotrope specification.
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.
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Cao
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Luan
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|Department of Cell Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: An-Jun
authors.initials: AJ
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, Texas 78245, USA.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathophysiology, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China.
authors.forename: Guang-Xia
authors.initials: GX
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Dajin
authors.initials: D
authors.lastname: Zou
authors.affiliation: National Key Laboratory of Molecular Biology and Department of Immunology, Chinese Academy of Medical Sciences, 9 Dongdan Santiao, Beijing, 100005, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Grusby
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|Department of Cell Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Weiping J
authors.initials: WJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019070:Cell Lineage / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D007018:Hypopituitarism / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D052682:Lactotrophs / Q000166:cytology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010903:Pituitary Gland, Anterior / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D011388:Prolactin / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D014157:Transcription Factors; C520426:Zbtb20 protein, mouse; D011388:Prolactin