Document Detail


Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells.
MedLine Citation:
PMID:  21822295     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Late-onset hypogonadism (LOH) is closely related to secondary androgen deficiency in aged males, but the mechanism remains unclear. In this study, we found that reduced testosterone production in aged rat Leydig cells is associated with decreased autophagic activity. Primary rat Leydig cells and the TM3 mouse Leydig cell line were used to study the effect of autophagic deficiency on Leydig cell testosterone production. In Leydig cells from young and aged rats, treatment with wortmannin, an autophagy inhibitor, inhibited luteinising hormone (LH)-stimulated steroidogenic acute regulatory (StAR) protein expression and decreased testosterone production. In contrast, treatment with rapamycin, an autophagy activator, enhanced LH-stimulated steroidogenesis in Leydig cells from aged, but not young, rats. Intracellular reactive oxygen species (ROS) levels were increased in both young and aged Leydig cells treated with wortmannin but decreased only in aged Leydig cells treated with rapamycin. Furthermore, an increased level of ROS, induced by H(2)O(2), resulted in LH-stimulated steroidogenic inhibition. Finally, knockdown of Beclin 1 decreased LH-stimulated StAR expression and testosterone production in TM3 mouse Leydig cells, which were associated with increased intracellular ROS level. These results suggested that autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells, which might be influenced by intracellular ROS levels.
Authors:
Wei-Ren Li; Liang Chen; Zhi-Jie Chang; Hua Xin; Tao Liu; Yan-Quan Zhang; Guang-Yong Li; Feng Zhou; Yan-Qing Gong; Zhe-Zhu Gao; Zhong-Cheng Xin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-08
Journal Detail:
Title:  Asian journal of andrology     Volume:  13     ISSN:  1745-7262     ISO Abbreviation:  Asian J. Androl.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-07     Completed Date:  2012-02-27     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  100942132     Medline TA:  Asian J Androl     Country:  China    
Other Details:
Languages:  eng     Pagination:  881-8     Citation Subset:  IM    
Affiliation:
Andrology Center, Peking University First Hospital, Peking University, Beijing 100034, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis Regulatory Proteins / genetics
Autophagy*
Blotting, Western
Cells, Cultured
Gene Knockdown Techniques
Leydig Cells / cytology,  immunology*,  metabolism
Luteinizing Hormone / physiology
Male
Mice
Microscopy, Electron, Transmission
Phosphoproteins / metabolism
Radioimmunoassay
Rats
Rats, Wistar
Reactive Oxygen Species / metabolism
Testosterone / biosynthesis,  metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Becn1 protein, mouse; 0/Phosphoproteins; 0/Reactive Oxygen Species; 0/steroidogenic acute regulatory protein; 58-22-0/Testosterone; 9002-67-9/Luteinizing Hormone
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