Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells

Abstract Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D 2 (PGD 2 ) system in Sertoli cells. Now, we found that PGD 2 increases ROS and hydrogen peroxide (H 2 O 2 ) generation in murine TM4 Sertoli cells, and also induces antioxidant enzymes expression suggesting that defense systems are triggered as an adaptive stress mechanism that guarantees cell survival. ROS and specially H 2 O 2 may act as second messengers regulating signal transduction pathways and gene expression. We describe a stimulatory effect of PGD 2 on lactate dehydrogenase (LDH) expression via DP1/DP2 receptors, which is prevented by the antioxidant N -acetyl-L-cysteine and the PI3K / Akt pathway inhibitor LY 294002. PGD 2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide evidence for a role of PGD 2 in the regulation of the oxidant/antioxidant status in Sertoli cells and, more importantly, in the modulation of LDH expression which takes place through ROS generation and the Akt-CREB / ATF-1 pathway.