胎儿和新生儿16α -羟基类固醇和皮质类固醇的合成和代谢

S. Takagi, K. Den
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引用次数: 1

摘要

本研究涉及胎儿体内一系列16α-羟基类固醇、糖皮质激素和矿皮质激素的生物合成和代谢及其在母胎血浆和羊水中的浓度。在16-20周的胎儿中,分布在微粒体部分的肾上腺中的16α-羟基类固醇、17α-羟化酶和c17 - 20-裂解酶以及肝脏中的16α-羟化酶的生物合成具有极高的活性。在105,000xg上清部分中也发现了较高的硫激酶活性,其活性依次为肾上腺、肝脏和小肠。这些酶的活性受到脐带血浆中存在的一些类固醇的影响。在糖皮质激素和矿皮质激素的生物合成中,17α-、21-羟化酶分布在终肾上腺皮质的线粒体外部分,而11β-、18-羟化酶和18-脱氢酶分布在线粒体部分。所有这些酶在妊娠早期都表现出较高的活性,血管紧张素- ii对11β-、18-羟化酶和钾有选择性刺激,同时ACTH对18-脱氢酶有选择性刺激。所有16α-羟基类固醇在胎儿血浆中始终高于母体血浆,并在妊娠晚期显示出2至4倍的增加。所有的皮质类固醇在胎儿血浆中也较高,并在此期间增加。已经确定的是,一部分皮质醇经过硫酸盐偶联或转化为四氢衍生物,醛固酮主要转化为3α' 5β-四氢醛固酮,一部分进行葡萄糖糖苷化。因此,在胎儿体内,一些营养激素和内源性类固醇在控制16α-羟基类固醇和皮质类固醇的生物合成和代谢中变得活跃。同时,血液中存在的蛋白质结合、非结合组分以及硫酸盐或葡萄糖醛酸盐结合、非结合组分倾向于维持平衡并控制这些系统。
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Synthesis and Metabolism of 16α‐Hydroxy‐Steroids and Corticosteroids in Fetuses and Neonates
This study involved the biosynthesis and metabolism of a series of 16α-hydroxy-steroids and gluco- and mineralocorticoids in the fetus and their concentrations in materno-fetal plasma and amniotic fluid. In the biosynthesis of 16α-hydroxy-steroids, 17α-hydroxylase and C17–20-lyase in the adrenals and 16α-hydroxylase in the liver which are distributed in the microsomal fractions, extremely high activities are observed in 16–20 week fetuses. High sulfokinase activity is also found in the 105,000xg supernatant fraction and the activity in decreasing order is adrenal, liver and small intestine. These enzyme activities are affected by some steroids present in the umbilical plasma. In the biosynthesis of gluco- and mineralocorticoids, 17α-, 21-hydroxylase are distributed in the extramitochondrial fraction of the definitive adrenal cortex while 11β-, 18-hydroxylase and 18-dehydrogenase are in the mitochondrial fraction. All of these enzymes show high activities relatively early in gestation and angiotensin-II shows a selective stimulation for 11β-, 18-hydroxylase and potassium together with ACTH for 18-dehydrogenase. All of the 16α-hydroxy-steroids are consistently higher in the fetal plasma than in maternal plasma and show a 2 to 4 fold increase during the 3rd trimester of gestation. All of corticosteroids assayed are also higher in the fetal plasma and increase during this period. It is well established that a portion of cortisol undergoes sulfate conjugation or conversion to tetrahydro-derivative and that aldosterone is largely converted to 3α' 5β-tetrahydro-aldosterone and a portion undergoes glucosiduronation. Thus, in the fetus, some trophic hormones and endogenous steroids become active in the control of 16α-hydroxy-steroid and corticosteroid biosynthesis and metabolism. In conjunction, the presence of protein bound, unbound fractions as well as sulfate or glucuronide conjugated, unconjugated fractions in the blood tends to maintain an equilibrium and control over these systems.
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