Benediktsson R, Calder A A, Edwards C R, Seckl J R
University Department of Medicine, Western General Hospital, Edinburgh, Scotland, UK.
Clin Endocrinol (Oxf). 1997 Feb;46(2):161-6. doi: 10.1046/j.1365-2265.1997.1230939.x.
Placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11 beta-HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas.
Placentas were obtained from randomly selected normal term deliveries. The maternal circuit was perfused with physiological concentration of cortisol, the fetal effluent collected and steroid metabolites separated and quantified using silica columns (Sep-pak Plus) and HPLC.
Most of the maternally administered cortisol was metabolized to cortisone, and no conversion of cortisone to cortisol was detected. Cortisone was the only product of cortisol metabolism. Inhibition of 11 beta-HSD with glycyrrhetinic acid allowed cortisol to gain direct access to the fetal circulation.
We conclude that human placental 11 beta-HSD plays a crucial role in controlling glucocorticoid access to the fetus. Other enzymes are not significant contributors at physiologically relevant cortisol concentrations.
胎盘11β-羟类固醇脱氢酶（11β-HSD）可将活性皮质醇转化为无活性的可的松，有人提出这是保护胎儿免受母体糖皮质激素生长抑制作用的机制；然而，其他胎盘酶也与此有关。胎盘11β-HSD在体外不稳定，因此检测到的酶活性可能与所提出的屏障作用无关。因此，我们研究了新鲜分离的完整人胎盘双灌注中的糖皮质激素代谢。
胎盘取自随机选择的足月正常分娩。母体循环用生理浓度的皮质醇灌注，收集胎儿流出物，使用硅胶柱（Sep-pak Plus）和高效液相色谱法分离并定量类固醇代谢物。
大部分母体给予的皮质醇代谢为可的松，未检测到可的松向皮质醇的转化。可的松是皮质醇代谢的唯一产物。用甘草次酸抑制11β-HSD可使皮质醇直接进入胎儿循环。
我们得出结论，人胎盘11β-HSD在控制糖皮质激素进入胎儿方面起关键作用。在生理相关的皮质醇浓度下，其他酶的作用不显著。
