Heme oxygenase-carbon monoxide (HO-CO) system in rat uterus: effect of sexual steroids and prostaglandins

Pregnancy maintenance is a very complex phenomenon, and the mechanisms that allow the survival of the fetus within the maternal uterus are still poorly understood. Our objectives were to analyze heme oxygenase (HO) activity and expression in the pregnant rat and to study its association with steroid hormones and prostaglandins. Uterine tissues were obtained from non-pregnant and from time-mated rats at days 5, 13, 18-22 of pregnancy and postpartum. HO activity was significantly higher at days 5 and 20 while HO-1 protein levels measured by Western blot, were significantly elevated from days 19 to 22. In ovariectomized rats, estrogen and progesterone in estrogenized animals increased HO activity and expression. Cyclooxygenase inhibitors augmented HO activity and HO-1 expression. Pre-incubation with prostaglandin F2alpha (PGF2alpha) diminished the enzymatic activity in ovariectomized rat uterus. Tin protoporphyrin IX, an HO inhibitor, significantly decreased uterine cGMP accumulation. Bilirubin decreased uterine thiobarbituric acid substances levels (an index of lipid peroxidation). These results demonstrate a uterine gestational pattern of HO activity and expression in the rat. In addition, these results suggest that uterine HO activity could regulate uterine quiescence in pregnancy via cGMP and it may contribute to the defense against oxidative stress.