Food intake, tumor growth, and weight loss in EP(2) receptor subtype knockout mice bearing PGE(2)-producing tumors

Previous studies in our laboratory have demonstrated that prostaglandin (PG) E(2) is involved in anorexia/cachexia development in MCG 101 tumor-bearing mice. In the present study, we investigate the role of PGE receptor subtype EP(2) in the development of anorexia after MCG 101 implantation in wild-type (EP(2)(+/+)) or EP(2)-receptor knockout (EP2(−/−)) mice. Our results showed that host absence of EP(2) receptors attenuated tumor growth and development of anorexia in tumor-bearing EP(2) knockout mice compared to tumor-bearing wild-type animals. Microarray profiling of the hypothalamus revealed a relative twofold change in expression of around 35 genes including mRNA transcripts coding for Phospholipase A(2) and Prostaglandin D(2) synthase (Ptgds) in EP(2) receptor knockout mice compared to wild-type mice. Prostaglandin D(2) synthase levels were increased significantly in EP(2) receptor knockouts, suggesting that improved food intake may depend on altered balance of prostaglandin production in hypothalamus since PGE(2) and PGD(2) display opposing effects in feeding control.