Document Detail


Essential roles of androgen signaling in Wolffian duct stabilization and epididymal cell differentiation.
MedLine Citation:
PMID:  21303954     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The epididymis is a male accessory organ and functions for sperm maturation and storage under the control of androgen. The development of the epididymis is also androgen dependent. The Wolffian duct (WD), anlagen of the epididymis, is formed in both male and female embryos; however, it is stabilized only in male embryos by testicular androgen. Androgen drives subsequent differentiation of the WD into the epididymis. Although the essential roles of androgen in WD masculinization and epididymal function have been established, little is known about cellular events regulated precisely by androgen signaling during these processes. It is also unclear whether androgen signaling, especially in the epithelia, has further function for epididymal epithelial cell differentiation. In this study we examined the cellular death and proliferation controlled by androgen signaling via the androgen receptor (AR) in WD stabilization. Analyses using AR knockout mice revealed that androgen signaling inhibits epithelial cell death in this process. Analysis of AP2α-Cre;AR(flox/Y) mice, in which AR function is deleted in the WD epithelium, revealed that epithelial AR is not required for the WD stabilization but is required for epithelial cell differentiation in the epididymis. Specifically, loss of epithelial AR significantly reduced expression of p63 that is essential for differentiation of basal cells in the epididymal epithelium. We also interrogated the possibility of regulation of the p63 gene (Trp63) by AR in vitro and found that p63 is a likely direct target of AR regulation.
Authors:
Aki Murashima; Shinichi Miyagawa; Yukiko Ogino; Hisayo Nishida-Fukuda; Kimi Araki; Takahiro Matsumoto; Takehito Kaneko; Kazuya Yoshinaga; Ken-ichi Yamamura; Takeshi Kurita; Shigeaki Kato; Anne M Moon; Gen Yamada
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-08
Journal Detail:
Title:  Endocrinology     Volume:  152     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-24     Completed Date:  2011-05-23     Revised Date:  2012-10-30    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1640-51     Citation Subset:  AIM; IM    
Affiliation:
Institute of Molecular Embryology and Genetics, Graduate School of Medical and Pharmaceutical Sciences, Global Center of Excellence Cell Fate Regulation Research and Education Unit, Kumamoto University, Kumamoto 860-0811, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics,  physiology
Cell Differentiation / genetics,  physiology
Cell Proliferation
Epididymis / cytology*,  embryology,  transplantation
Female
Immunohistochemistry
Male
Mice
Mice, Knockout
Mice, Nude
Phosphoproteins / genetics,  metabolism*
Pregnancy
Receptors, Androgen / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Trans-Activators / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 CA154358/CA/NCI NIH HHS; R01 HD046767-02/HD/NICHD NIH HHS; R01 HD046767-03/HD/NICHD NIH HHS; R01 HD046767-04/HD/NICHD NIH HHS; R01CA154358-01/CA/NCI NIH HHS; R01ES016597-01A1/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Phosphoproteins; 0/Receptors, Androgen; 0/Trans-Activators; 0/Trp63 protein, mouse
Comments/Corrections

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