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Title 

Phosphoenolpyruvate carboxykinase and glucose-6-phosphatase are required for steroidogenesis in testicular leydig cells

Authors 

S W AhnGil Tae GangS TadiB NedumaranY D KimJ H ParkG R KweonS H KooK LeeR S AhnY H YimChul Ho LeeR A HarrisH S Choi

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2012

Citation 

Journal of Biological Chemistry, vol. 287, no. 50, pp. 41875-41887

Abstract 

Cyclic AMP (cAMP) induces steroidogenic enzyme gene expression and stimulates testosterone production in Leydig cells. Phosphoenolpyruvate carboxykinase (PEPCK) is expressed in Leydig cells, but its role has not been defined. In this study, we found that PEPCK and glucose-6-phosphatase (Glc-6-Pase) are increased significantly following cAMP treatment of mouse Leydig cells. Moreover, cAMP treatment increased recruitment of the cAMP-response element-binding transcription factor and decreased recruitment of the corepressor DAX-1 on the pepck promoter. Furthermore, cAMP induced an increase in ATP that correlated with a decrease in phospho- AMP-activated protein kinase (AMPK). In contrast, knockdown or inhibition of PEPCK decreased ATP and increased phospho- AMPK. Treatment with an AMPK activator or overexpression of the constitutively active form of AMPK inhibited cAMP-induced steroidogenic enzyme promoter activities and gene expression. Liver receptor homolog-1 (LRH-1) was involved in cAMP-induced steroidogenic enzyme gene expression but was inhibited by AMPK activation in Leydig cells. Additionally, inhibition or knockdown of PEPCK and Glc-6-Pase decreased cAMP-mediated induction of steroidogenic enzyme gene expression and steroidogenesis. Finally, pubertal mouse (8-week-old) testes and human chorionic gonadotropin-induced prepubertal mouse testes showed increased PEPCK and Glc-6-Pase gene expression. Taken together, these results suggest that induction of PEPCK and Glc-6-Pase by cAMP plays an important role in Leydig cell steroidogenesis. -------------------------------------------------------------------------------- Reaxys Database Information; --------------------------------------------------------------------------------

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M112.421552

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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