Klemcke H G, Christenson R K
USDA-ARS, Roman L. Hruska U.S. Meat Animal Research Center, Clay Center, Nebraska 68933-0166, USA.
Biol Reprod. 1996 Jul;55(1):217-23. doi: 10.1095/biolreprod55.1.217.
The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-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 11 beta-HSD oxidative activity (conversion of cortisol to cortisone), to measure effects of gestational age and uterine environment on 11 beta-HSD, and to determine any associations between placental 11 beta-HSD and fetal size. Characterization of placental 11 beta-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" (< or = 20 cm/potential embryo) or "roomy" (> or = cm/potential embryo). Fetal weight and length were increased (p < or = 0.015) in the roomy compared with the crowded uterine environment at each gestational age. Both NADP(+)- and NAD(+)-dependent 11 beta-HSD increased almost fivefold between 50 and 100 days of gestation (p < 0.02). At each gestational age, the amount of NAD(+)-dependent 11 beta-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 11 beta-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 11 beta-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.
11β-羟基类固醇脱氢酶（11β-HSD）可将具有生物活性的皮质醇可逆地转化为无活性的可的松，胎盘内的该酶可能起到保护胎儿免受高浓度母体糖皮质激素影响的作用。开展了多项实验，以表征胎盘11β-HSD的氧化活性（将皮质醇转化为可的松），测定胎龄和子宫环境对11β-HSD的影响，并确定胎盘11β-HSD与胎儿大小之间的关联。对妊娠100天时的胎盘11β-HSD进行表征显示存在两种不同的同工型，一种依赖于NADP(+)，另一种依赖于NAD(+)。推测的依赖于NAD(+)的同工型具有较低的米氏常数（纳摩尔范围）和较高的最大反应速度，可能在生物学上更具相关性。然后在妊娠50、75和100天时从子宫环境中获取胎盘，这些子宫环境在妊娠第2天进行子宫结扎后，要么是“拥挤的”（≤20厘米/潜在胚胎），要么是“宽松的”（≥ 厘米/潜在胚胎）。在每个胎龄时，与拥挤的子宫环境相比，宽松子宫环境中的胎儿体重和体长增加（p≤0.015）。依赖于NADP(+)和NAD(+)的11β-HSD在妊娠50至100天之间均增加了近五倍（p<0.02）。在每个胎龄时，依赖于NAD(+)的11β-HSD的量比依赖于NADP(+)的11β-HSD的量高出两倍多（p<0.001）。胎龄、子宫环境和胎儿性别之间存在显著的统计学交互作用，表明这些因素对胎盘11β-HSD活性的影响是复杂的。当考虑与实验模型相关的所有因素时，胎儿或胎盘大小与胎盘11β-HSD活性之间没有显著关联。这些发现证明了猪胎盘11β-HSD活性的存在，提示存在两种同工型，表明了胎龄的影响，并提示了子宫环境和胎儿性别对这些活性的影响。
