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胆固醇侧链裂解细胞色素P450、细胞色素P450 17α-羟化酶/17,20-裂解酶和3β-羟类固醇脱氢酶异构酶等类固醇生成酶在人和恒河猴胎儿肾上腺中的定位:对功能分区的重新评估

Localization of cytochrome P450 cholesterol side-chain cleavage, cytochrome P450 17 alpha-hydroxylase/17, 20-lyase, and 3 beta-hydroxysteroid dehydrogenase isomerase steroidogenic enzymes in human and rhesus monkey fetal adrenal glands: reappraisal of functional zonation.

作者信息

Mesiano S, Coulter C L, Jaffe R B

机构信息

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143.

出版信息

J Clin Endocrinol Metab. 1993 Nov;77(5):1184-9. doi: 10.1210/jcem.77.5.8077311.

DOI:10.1210/jcem.77.5.8077311
PMID:8077311
Abstract

We examined the in situ localization of key steroidogenic enzymes in adrenal gland sections from midgestation (17-24 weeks) human fetuses and late gestation (130-142 days; term = 165 days) rhesus monkey fetuses. The rhesus monkey fetal adrenals were used as a model for the late gestation human fetal adrenal. The enzymes examined were cytochrome P450 cholesterol side-chain cleavage (P450scc), cytochrome P450 17 alpha-hydroxylase/17,20-lyase (P450c17), and 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD). In human fetal adrenals, P450scc and P450c17 proteins and mRNAs were detected only in fetal zone (innermost cortical zone) and transitional zone (between the fetal and definitive zone) cells, not in definitive zone cells. Expression of 3 beta HSD was not detected in any cortical zone cells in midgestation human fetal adrenals. In rhesus monkey fetal adrenals, a similar pattern of P450scc and P450c17 expression was observed in the fetal and transitional zones. In the definitive zone cells of rhesus monkey fetal adrenals, expression of both P450scc and 3 beta HSD was detected. In addition, low levels of 3 beta HSD expression could be detected in some transitional zone cells. P450c17 expression was lacking in definitive zone cells from rhesus monkey fetal adrenals. These data suggest that early in gestation, cortisol is not produced by the human fetal adrenal cortex in vivo (because it does not express 3 beta HSD), whereas androgen production occurs in the transitional and fetal zones (which express P450scc and P450c17). Later in gestation, the definitive zone may produce minearlocorticoids (because it expresses P450scc and 3 beta HSD, but lacks P450c17), and the transitional zone may produce glucocorticoids (it expresses P450scc, P450c17, and 3 beta HSD), whereas the fetal zone continues to produce androgens. Thus, late in gestation the functional zonation of the human fetal adrenal cortex may be similar to that of the adult, with the definitive zone being analogous to the nascent zona glomerulosa, the transitional zone analogous to the zona fasciculata, and the fetal zone analogous to the zona reticularis.

摘要

我们检测了妊娠中期(17 - 24周)人类胎儿以及妊娠晚期(130 - 142天;足月为165天)恒河猴胎儿肾上腺切片中关键类固醇生成酶的原位定位。恒河猴胎儿肾上腺被用作妊娠晚期人类胎儿肾上腺的模型。所检测的酶包括细胞色素P450胆固醇侧链裂解酶(P450scc)、细胞色素P450 17α - 羟化酶/17,20 - 裂解酶(P450c17)和3β - 羟类固醇脱氢酶/异构酶(3βHSD)。在人类胎儿肾上腺中,P450scc和P450c17蛋白及mRNA仅在胎儿带(最内层皮质带)和过渡带(胎儿带与永久带之间)的细胞中检测到,而在永久带细胞中未检测到。在妊娠中期人类胎儿肾上腺的任何皮质带细胞中均未检测到3βHSD的表达。在恒河猴胎儿肾上腺中,在胎儿带和过渡带观察到了类似的P450scc和P450c17表达模式。在恒河猴胎儿肾上腺的永久带细胞中,检测到了P450scc和3βHSD的表达。此外,在一些过渡带细胞中可检测到低水平的3βHSD表达。恒河猴胎儿肾上腺永久带细胞中缺乏P450c17表达。这些数据表明,在妊娠早期,人类胎儿肾上腺皮质在体内不产生皮质醇(因为其不表达3βHSD),而雄激素在过渡带和胎儿带产生(这两个带表达P450scc和P450c17)。在妊娠后期,永久带可能产生盐皮质激素(因为其表达P450scc和3βHSD,但缺乏P450c17),过渡带可能产生糖皮质激素(其表达P450scc、P450c17和3βHSD),而胎儿带继续产生雄激素。因此,在妊娠后期,人类胎儿肾上腺皮质的功能分区可能与成人相似,永久带类似于新生的球状带,过渡带类似于束状带,胎儿带类似于网状带。

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