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PMID: 21303954 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Essential roles of androgen signaling in Wolffian duct stabilization and epididymal cell differentiation.

Endocrinology ·Vol. 152 ·No. 4 ·2011-04-00 ·Pages 1640-51

Murashima A, Miyagawa S, Ogino Y, Nishida-Fukuda H, Araki K, Matsumoto T, Kaneko T, Yoshinaga K, Yamamura K, Kurita T, Kato S, Moon AM, Yamada G

Abstract

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.

MeSH Terms
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
Chemicals
Phosphoproteins Receptors, Androgen Trans-Activators Trp63 protein, mouse
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Murashima Aki
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.
Miyagawa Shinichi
Ogino Yukiko
Nishida-Fukuda Hisayo
Araki Kimi
Matsumoto Takahiro
Kaneko Takehito
Yoshinaga Kazuya
Yamamura Ken-ichi
Kurita Takeshi
Kato Shigeaki
Moon Anne M
Yamada Gen
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Article Info
Journal
Endocrinology
Abbr.
Endocrinology
ISSN
1945-7170
DOI
10.1210/en.2010-1121
Published
2011-04-00
Epub
2011-00-08
Pages
1640-51
Language
English
Region
United States
NLM ID
0375040
PMCID
PMC3060634
Subset
IM
Grants
NIEHS NIH HHS · R01 ES016597 · United States
NICHD NIH HHS · R01 HD046767-03 · United States
NICHD NIH HHS · R01 HD046767-02 · United States
NICHD NIH HHS · R01 HD046767-04 · United States
NICHD NIH HHS · R01 HD046767 · United States
NIEHS NIH HHS · R01ES016597-01A1 · United States
NCI NIH HHS · R01CA154358-01 · United States
NCI NIH HHS · R01 CA154358 · United States
External Links
PubMed source DOI: 10.1210/en.2010-1121 PMC Full Text View journal details
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