Abstract #449

# 449
Interferon-tau and progesterone down-regulate cytochrome P450 1A and 2C in bovine endometrial epithelial cells.
Caleb O. Lemley*1, Christa L. Gilfeather1, 1Mississippi State University, Mississippi State, MS.

The objective of the current study was to examine cytochrome P450 1A (CYP1A) and 2C (CYP2C) activity in bovine endometrial cell cultures following exposure to oxytocin (OT), interferon-tau (IFN), estradiol (E2), and/or progesterone (P4). Bovine endometrial epithelial cells were cultured to 80% confluence in 6-well plates. For experiment 1, cells were treated with 1 µg/mL OT, 10 ng/mL IFN, a combination of OT+IFN, or control (CON) media for 24 h. For the second experiment, cells were treated with 1 ng/mL E2, 15 ng/mL P4, a combination of E2+P4, or CON media for 24 h. Following the hormone treatment, endometrial cells were harvested in lysis buffer containing protease and phosphatase inhibitors and frozen at −80°C until further analysis. Treatments were performed in triplicate and the experiment was repeated 4 times (n = 12 per treatment). The activity of CYP1A and CYP2C were determined using specific luminogenic substrates and expressed relative to mg of cellular protein. Data were analyzed using MIXED procedure of SAS and the model statement included hormone and replicate. Treatment with OT alone did not alter activity of CYP1A (P = 0.55) or CYP2C (P = 0.46) compared with CON cells. Activity of CYP1A was decreased in cells exposed to IFN (P < 0.01) or OT+IFN (P < 0.01) compared with CON. Similarly, activity of 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 cells. Activity of CYP1A was decreased (P < 0.01) in P4 versus CON, while E2+P4 was not different (P = 0.38) from CON. Activity of CYP2C was decreased in cells exposed to P4 (P < 0.01) or E2+P4 (P < 0.01) compared with CON cells. In summary, both interferon-tau and progesterone exposure decreased CYP1A and CYP2C activity. The mixed function monooxygenase enzymes, CYP1A and CYP2C, have been implicated in synthesizing embryotoxic compounds; therefore, down-regulation in the endometrium may be necessary during maternal recognition of pregnancy.

Key Words: cytochrome P450, endometrium, interferon-tau