Phosphoenolpyruvate carboxykinaseandglucose-6-phosphatase are required for steroidogenesis in testicular leydig cells

Seung Won Ahn, Gil Tae Gang, Surendar Tadi, Balachandar Nedumaran, Yong Deuk Kim, Ji Hoon Park, Gi Ryang Kweon, Seung Hoi Koo, Keesook Lee, Ryun Sup Ahn, Yong Hyeon Yim, Chul Ho Lee, Robert A. Harris, Hueng Sik Choi

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16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)41875-41887
Number of pages13
JournalJournal of Biological Chemistry
Volume287
Issue number50
DOIs
Publication statusPublished - 2012 Dec 7

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ahn, S. W., Gang, G. T., Tadi, S., Nedumaran, B., Kim, Y. D., Park, J. H., Kweon, G. R., Koo, S. H., Lee, K., Ahn, R. S., Yim, Y. H., Lee, C. H., Harris, R. A., & Choi, H. S. (2012). Phosphoenolpyruvate carboxykinaseandglucose-6-phosphatase are required for steroidogenesis in testicular leydig cells. Journal of Biological Chemistry, 287(50), 41875-41887. https://doi.org/10.1074/jbc.M112.421552