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. PPARalpha and PPARdelta, but not PPARgamma, mRNAs are expressed in the BEND cell line regardless of treatment. Under resting conditions, PPARalpha mRNA levels increase in response to growth hormone (P < 0.05). In cells stimulated with PdBu, growth hormone depresses PPARalpha mRNA levels, regardless of whether cells also are treated with IFNtau. In contrast, PPARdelta mRNA levels are increased by exposure to PdBu, eicosapentanoic acid and IFNtau, and these effects are additive. PPAR mRNA levels are not predictive of prostaglandin accumulation. Agonist activation of PPARalpha, PPARdelta or PPARgamma augments PdBu-induced increases in prostaglandin H synthase-2 mRNA and media accumulation of prostaglandins F2alpha and E2. Treatment with the PPARalpha/delta agonist carbaprostacyclin, but not the PPARalpha agonist Wy14643 or PPARgamma agonist ciglitazone, completely reverses the IFNtau suppression of prostaglandin synthesis. In conclusion, PPARalpha and PPARdelta function in the response of bovine endometrium to growth hormone and long chain omega-3 polyunsaturated fatty acids.