Porcine placental 11 beta-hydroxysteroid dehydrogenase activity

The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) reversibly converts biologically active cortisol to inactive cortisone, and when present in placentae may act to protect fetuses from high concentrations of maternal glucocorticoids. Experiments were conducted to characterize placental 11beta-HSD oxidative activity (conversion of cortisol to cortisone), to measure effects of gestational age and uterine environment on 11beta-HSD, and to determine any associations between placental 11 beta-HSD and fetal size. Characterization of placental 11beta-HSD at 100 days of gestation suggests the presence of two different isoforms, one that is NADP+-dependent and a second that is NAD+-dependent. The putative NAD+-dependent isoform has a lower Km (nM range) and a greater Vmax, and is likely to be more biologically relevant. Placentae were then obtained at 50, 75, and 100 days of gestation from uterine environments that subsequent to uterine ligations on Day 2 of gestation were either "crowded" (less than or equal to 20 cm/potential embryo) or "roomy" (greater than or equal to 25 cm/potential embryo). Fetal weight and length were increased (p less than or equal to 0.015) in the roomy compared with the crowded uterine environment at each gestational age. Both NADP+- and NAD+-dependent 11beta-HSD increased almost fivefold between 50 and 100 days of gestation (p < 0.02). At each gestational age, the amount of NAD+-dependent 11beta-HSD was over twofold greater (p < 0.001) than that of NADP+-dependent 11 beta-HSD. Significant statistical interactions among gestational age, uterine environment, and fetal sex indicate that the effects of these factors on placental 11beta-HSD activity are complex. When all factors associated with the experimental model were taken into account, there were no significant associations between fetal or placental size and placental 11 beta-HSD activity. These findings demonstrate the existence of porcine placental 11beta-HSD activity, suggest the presence of two isoforms, indicate effects of gestational age, and suggest effects of uterine environment and fetal sex on these activities.