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猴胎儿肾上腺皮质激素的形成:17-、21-和11-羟化酶活性的评估

Corticoid formation by the monkey fetal adrenal: evaluation of 17-, 21-, and 11-hydroxylase activities.

作者信息

Sholl S A

出版信息

Steroids. 1982 Oct;40(4):475-85. doi: 10.1016/0039-128x(82)90024-1.

DOI:10.1016/0039-128x(82)90024-1
PMID:7170754
Abstract

There is indirect evidence that cortisol synthesis in the fetal rhesus monkey adrenal gland is limited at Day 135 of gestation but increases thereafter. This study was conducted to ascertain whether a reduced synthetic capacity is caused by a deficiency in 17-, 21- or 11-hydroxylase activity. For the sake of comparison 11- and 21-hydroxylases were also estimated in adult adrenals. 11-, 21-Hydroxylases were measured in the entire adrenal by the oxidation of NADPH by mitochondria and microsomes, respectively. 17-Hydroxylase was evaluated in outer and inner regions of the fetal gland by the formation of [3H]17-hydroxyprogesterone, -11-deoxycortisol, -cortisol and -androstenedione from [3H]progesterone. The maximum velocity of both the 11- and 21-hydroxylase was similar in fetal and adult glands indicating that corticoid formation in the fetus is not constrained by levels of these enzymes. [3H]Progesterone was extensively metabolized to -17-hydroxyprogesterone, -androstenedione, -11-deoxycortisol and -cortisol by homogenates from both regions of the fetal adrenal. The ratio of [3H]-cortisol to [3H]11-deoxycortisol was consistently higher in incubations of the inner glandular area. Together, these findings indicate that 17-hydroxylase is also active at Day 135 and that the 11-hydroxylase may be more concentrated in the fetal cortex. These data suggest in addition that the restriction in cortisol formation occurs at a step prior to the metabolism of progesterone to cortisol.

摘要

有间接证据表明,妊娠135天时,恒河猴胎儿肾上腺皮质醇的合成受限,但此后会增加。本研究旨在确定合成能力降低是否是由17-、21-或11-羟化酶活性不足引起的。为了进行比较,还对成年肾上腺中的11-和21-羟化酶进行了评估。分别通过线粒体和微粒体氧化NADPH来测定整个肾上腺中的11-、21-羟化酶。通过[3H]孕酮生成[3H]17-羟孕酮、-11-脱氧皮质醇、-皮质醇和-雄烯二酮,对胎儿肾上腺的外层和内层区域的17-羟化酶进行评估。胎儿和成年肾上腺中11-和21-羟化酶的最大反应速度相似,这表明胎儿体内皮质激素的形成不受这些酶水平的限制。来自胎儿肾上腺两个区域的匀浆可将[3H]孕酮广泛代谢为-17-羟孕酮、-雄烯二酮、-11-脱氧皮质醇和-皮质醇。在腺体内层区域的孵育中,[3H]-皮质醇与[3H]11-脱氧皮质醇的比值始终较高。这些发现共同表明,17-羟化酶在妊娠135天时也有活性,并且11-羟化酶可能在胎儿皮质中更为集中。此外,这些数据表明,皮质醇形成的限制发生在孕酮代谢为皮质醇之前的步骤。

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