title: cPGES/p23 is required for glucocorticoid receptor function and embryonic growth but not prostaglandin E2 synthesis.
abstract: A number of studies have identified cytosolic prostaglandin E(2) synthase (cPGES)/p23 as a cytoplasmic protein capable of metabolism of prostaglandin E(2) (PGE(2)) from the cyclooxygenase metabolite prostaglandin endoperoxide (PGH(2)). However, this protein has also been implicated in a number of other pathways, including stabilization of the glucocorticoid receptor (GR) complex. To define the importance of the functions assigned to this protein, mice lacking detectible cPGES/p23 expression were generated. cPGES/p23(-/-) pups die during the perinatal period and display retarded lung development reminiscent of the phenotype of GR-deficient neonates. Furthermore, GR-sensitive gluconeogenic enzymes are not induced in the prenatal period. However, unlike GR-deficient embryos, cPGES/p23(-/-) embryos are small and a proliferation defect is observed in cPGES/p23(-/-) fibroblasts. Analysis of arachidonic acid metabolites in embryonic tissues and primary fibroblasts failed to support a function for this protein in PGE(2) biosynthesis. Thus, while the growth retardation of the cPGES/p23(-/-) pups and decreased proliferation of primary fibroblasts identify functions for this protein in addition to GR stabilization, it is unlikely that these functions include metabolism of PGH(2) to PGE(2).
authors: University of North Carolina, Department of Genetics, Chapel Hill, NC 27599, USA.
authors: Alysia Kern
authors: AK
authors: Lovgren
authors: Martina
authors: M
authors: Kovarova
authors: Beverly H
authors: BH
authors: Koller
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D019085:Fluorescent Antibody Technique, Direct; D005456:Fluorescent Dyes; D019746:Intramolecular Oxidoreductases; D008099:Liver / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D008168:Lung / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000071876:Prostaglandin-E Synthases; D011453:Prostaglandins / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014162:Transfection
chemical_list: D005456:Fluorescent Dyes; D018832:Molecular Chaperones; D010750:Phosphoproteins; D011453:Prostaglandins; D011965:Receptors, Glucocorticoid; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D016650:Fluorescein-5-isothiocyanate; D015232:Dinoprostone