Peroxisome proliferator-activated receptor (PPAR) expression in cultured bovine endometrial cells and response to omega-3 fatty acid, growth hormone and agonist stimulation in relation to series 2 prostaglandin production

The peroxisome proliferator-activated receptors (PPARs) are a family of nuclear transcription factors thought to act as receptors for polyunsaturated fatty acids and to reduce production of series 2 prostaglandins (PG). The objectives of the current study were to characterize PPAR expression and the prostaglandin synthetic activity of cultured bovine endometrial cells in response to known PPAR ligands, as well as to key stimulators and inhibitors of series 2 prostaglandin secretion. PPARα and PPARδ, but not PPARγ, mRNAs are expressed in the BEND cell line regardless of treatment. Under resting conditions, PPARα mRNA levels increase in response to growth hormone (P < 0.05). In cells stimulated with PdBu, growth hormone depresses PPARα mRNA levels, regardless of whether cells also are treated with IFNτ. In contrast, PPARδ mRNA levels are increased by exposure to PdBu, eicosapentanoic acid and IFNτ, and these effects are additive. PPAR mRNA levels are not predictive of prostaglandin accumulation. Agonist activation of PPARα, PPARδ or PPARγ augments PdBu-induced increases in prostaglandin H synthase-2 mRNA and media accumulation of prostaglandins F2α and E2. Treatment with the PPARα/δ agonist carbaprostacyclin, but not the PPARα agonist Wy14643 or PPARγ agonist ciglitazone, completely reverses the IFNτ suppression of prostaglandin synthesis. In conclusion, PPARα and PPARδ function in the response of bovine endometrium to growth hormone and long chain omega-3 polyunsaturated fatty acids.