The role of phosphoenolpyruvate carboxykinase in neuronal steroidogenesis under acute inflammation

• We studied the effect of LPS on PEPCK and its role in neuronal steroidogenesis.
• LPS treatment significantly increased the mRNA expression of PEPCK in brain tissue.
• The mRNA expression of steroidogenic proteins were also increased in LPS treatment.
• Inhibition of PEPCK decreased the mRNA expression of steroidogenic proteins.
• PEPCK plays a pivotal role in neuronal steroidogenesis under inflammation.

Phosphoenolpyruvate carboxykinase (PEPCK) is a key gluconeogenic enzyme found in many tissues throughout the body including brain. In the present study, we have investigated the effect of bacterial lipopolysaccharide (LPS) on PEPCK and its role in neuronal steroidogenesis. Adult female albino rats were administered LPS (5 mg/kg body weight) to induce acute inflammation. LPS administration resulted in a significant increase of PEPCK mRNA expression with concomitant increase in mRNA levels of steroidogenic acute regulatory (StAR) protein and other steroidogenic enzymes including 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) and aromatase in brain tissue. Further, the inhibition of PEPCK expression by glipizide significantly decreased the mRNA expression of steroidogenic proteins and concurrently increased the mRNA levels of proinflammatory cytokines under LPS administration. The results of this study suggest a novel finding that PEPCK may have an important role in neuronal steroidogenesis; which serves as an adaptive response under inflammation.