Prostaglandins (PGs) play important roles in diverse physiological processes in the central nervous system. PGD(2) is the most abundant PG in the brain and acts through specific receptors, DP1 and CRTH2. We investigated the effects of PGD(2) on the morphology of the hypothalamic cell line mHypoE-N37 (N37). In N37 cells, serum starvation induced neurite outgrowth and PGD(2) elicited neurite retraction, although we failed to detect transcripts for DP1 and CRTH2. Such an effect of PGD(2) was efficiently mimicked by its metabolite, 15-deoxy-Delta(12,14)-prostaglandin J(2). N-acetyl cysteine completely abolished the effect of PGD(2), and reactive oxygen species (ROS) were considered to be important. Notably, neurite outgrowth was restored by PGD(2) removal. These results suggest that PGD(2) induces reversible neurite retraction in a ROS-mediated mechanism that does not involve any known receptor. (C) 2016 Elsevier Inc. All rights reserved.