During maternal recognition of pregnancy, the conceptus stimulates endometrial secretion of PGF(2)alpha and PGE(2). However, PGF(2)alpha is less effective in causing luteal regression in pregnant than in nonpregnant ewes. Experiments were conducted to elucidate mechanisms for reduced luteal sensitivity to PGF(2)alpha during maternal recognition of pregnancy. Corpora lutea (CL) were collected from pregnant and non-pregnant ewes 0, 4, or 12 h following treatment with PGF(2)alpha on day 12 after estrus. Luteal PTGHS2 mRNA did not differ due to PGF(2)alpha or pregnancy status. Luteal PTGES mRNA was reduced in both pregnant and non-pregnant ewes after PGF(2)alpha treatment; while, luteal PTGFS mRNA was reduced 4 h after PGF(2)alpha in pregnant, but not non-pregnant ewes. The result was a greater ratio of PTGES to PTGFS mRNA in pregnant ewes. Luteal mRNA for HPGD did not differ between pregnant and non-pregnant ewes on day 12. Luteal END1 mRNA was reduced in pregnant as compared to non-pregnant ewes prior to PGF(2)alpha challenge. Luteal END1 mRNA was increased after PGF(2)alpha in pregnant and non-pregnant ewes; however, ECEI mRNA was reduced 4 h after PGF(2)alpha in pregnant, but not non-pregnant ewes. The in vitro conversion of PGF(2)alpha to PGFM was greater in CL of pregnant than non-pregnant ewes at day 14. Luteal conversion of PGF(2)alpha to PGFM appears to be regulated posttranscriptionally. During maternal recognition of pregnancy, mechanisms of reduced luteal sensitivity to PGF(2)alpha may include a shift in prostaglandin production to the luteotropin PGE(2), a reduction of ECEI mRNA, and increased catabolism of PGF(2)alpha, (c) 2006 Elsevier Inc. All rights reserved.