Testosterone deficiency accompanied by testicular and epididymal abnormalities in TMF−/− mice

► TMF/ARA160 associates with the Golgi and ER organelles of testicular Leydig cells. ► Loss of TMF/ARA160 results in testicular and epididymal defects. ► Absence of TMF/ARA160 leads to a significantly decreased serum testosterone levels. ► External testosterone administration rescues epididymal apop...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2013-01, Vol.365 (1), p.52-63
Main Authors: Elkis, Yoav, Bel, Shai, Lerer-Goldstein, Tali, Nyska, Abraham, Creasy, Dianne M., Shpungin, Sally, Nir, Uri
Format: Article
Language:English
Subjects:
Abnormalities
Age Factors
Androgen
Animals
Apoptosis
blood serum
Cell Proliferation
Defects
Epididymis
Epididymis - abnormalities
Epididymis - metabolism
Epididymis - pathology
Gene Expression Profiling
Gene Expression Regulation
Hormone Replacement Therapy
Hormones
Leydig cells
Leydig Cells - enzymology
Leydig Cells - metabolism
Leydig Cells - pathology
luteinizing hormone
Luteinizing Hormone - blood
Male
Males
Mice
Mice, Inbred ICR
Mice, Knockout
Oligonucleotide Array Sequence Analysis
RNA, Messenger - metabolism
Serums
Spermatogenesis
spermatozoa
spermiogenesis
Stimulators
Testis
Testis - abnormalities
Testis - metabolism
Testis - pathology
Testosterone
Testosterone - blood
Testosterone - metabolism
Testosterone - therapeutic use
TMF/ARA160
Ubiquitin-Protein Ligases - deficiency
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Vesicular Transport Proteins - deficiency
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
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Summary:► TMF/ARA160 associates with the Golgi and ER organelles of testicular Leydig cells. ► Loss of TMF/ARA160 results in testicular and epididymal defects. ► Absence of TMF/ARA160 leads to a significantly decreased serum testosterone levels. ► External testosterone administration rescues epididymal apoptosis. ► TMF/ARA160 participates in the control of testosterone levels in mice. TMF/ARA160 is a Golgi-associated protein, which is essential for spermiogenesis. In this study, we show that lack of TMF/ARA160 leads to defects in both the testis and the epididymis. In the testis, spermatid retention and extensive proliferation of Leydig cells were observed. Concomitantly, the serum levels of luteinizing hormone (LH), a stimulator of Leydig cell proliferation, were significantly increased in TMF−/− mice. Structural and functional defects were also seen in the epididymis. These included apoptosis of epithelial epididymal cells and sperm stasis in the cauda. Notably, the serum testosterone levels of TMF−/− mice were significantly lower than those of wt mice, and external testosterone administration decreased the number of apoptotic epithelial epididymal cells in TMF−/− animals. In summary, we show here for the first time that TMF/ARA160 participates in the control of serum testosterone levels in males, and its absence results in major testicular and epididymal defects.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2012.09.003