Effects of Interferon-Tau and Steroids on Cytochrome P450 Activity in Bovine Endometrial Epithelial Cells.

Abstract

The objective of the current study was to examine cyclooxygenase (COX), cytochrome P450 1A (CYP1A) and 2C (CYP2C) activity in bovine endometrial cell cultures following exposure to oxytocin (OT), interferon-τ (IFN), estradiol (E2) and/or progesterone (P4). Bovine endometrial epithelial cells were treated with OT, IFN, a combination of OT+IFN or control (CON) media for 24h. For the second experiment, cells were treated with E2, P4, a combination of E2+P4 or CON media for 24h. Treatments were performed in triplicate, and the experiment was repeated four times (n=12 per treatment). Treatment with OT alone increased (p<0.01) activity of COX compared with CON; however, OT alone did not alter activity of CYP1A (p=0.55) or CYP2C (p=0.46) compared with CON. Activity of CYP1A and CYP2C was decreased in cells exposed to IFN (p<0.01) or OT+IFN (p<0.01) compared with CON. Treatment with E2 alone did not alter activity of CYP1A (p=0.64) or CYP2C (p=0.06) compared with CON. Activity of CYP1A and CYP2C was decreased (p<0.01) in P4 vs CON. In summary, IFN exposure, irrespective of OT treatment, decreased the activity of CYP1A and CYP2C. Activity of CYP1A was decreased following P4 treatment alone, while that of CYP2C was decreased following both P4 and E2+P4 treatment. The mixed function monooxygenase enzymes, CYP1A and CYP2C, have been implicated in synthesizing embryotoxic compounds; therefore, downregulation in the endometrium may be necessary during maternal recognition of pregnancy.