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. PPAR alpha and PPAR delta, but not PPAR-gamma, mRNAs are expressed in the BEND cell line regardless of treatment. Under resting conditions, PPAR alpha mRNA levels increase in response to growth hormone (P < 0.05). In cells stimulated with PdBu, growth hormone depresses PPAR alpha mRNA levels, regardless of whether cells also are treated with IFN tau. In contrast, PPAR delta mRNA levels are increased by exposure to PdBu, eicos-apentanoic acid and IFN tau, and these effects are additive. PPAR mRNA levels are not predictive of prostaglandin accumulation. Agonist activation of PPAR alpha, PPAR delta or PPAR gamma augments PdBu-induced increases in prostaglandin H synthase-2 mRNA and media accumulation of prostaglandins F-2 alpha and E-2. Treatment with the PPAR alpha/delta agonist carbaprostacyclin, but not the PPAR alpha agonist Wy14643 or PPAR gamma agonist ciglitazone, completely reverses the IFN tau suppression of prostaglandin synthesis. In conclusion, PPAR alpha and PPAR delta function in the response of bovine endometrium to growth hormone and long chain omega-3 polyunsaturated fatty acids. (c) 2005 Elsevier Inc. All rights reserved.