SF-1, DAX-1, and ACD: Molecular determinants of adrenocortical growth and steroidogenesis
SF-1, DAX-1, and ACD: Molecular determinants of adrenocortical growth and steroidogenesis
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DOI：
10.1081/erc-120016972
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发表时间：
2002-01-01
影响因子：
2.1
通讯作者：
Hammer, GD
中科院分区：
文献类型：
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作者：
Beuschlein, F;Keegan, CE;Hammer, GD
人类肾上腺皮质的形成是因为存在两个离散的区，胎儿区(FZ)在出生后不久退化，以及终止区(DZ)，它产生了成人皮质的经典类固醇生成区。小鼠拥有一种类似于FZ的结构，称为X区(YZ)，雄性在青春期退化，雌性在第一次怀孕期间退化。类似于人类FZ中由DAX-1(X染色体上剂量敏感性反转-肾上腺发育不良先天临界区)功能突变导致的X连锁先天性肾上腺发育不良，当DAX-1突变时，小鼠XZ不会退化。然而，只有在带有DAX-1突变的人类中，DZ才是小的和功能低下的。携带SF-I基因突变的患者和小鼠患有完全性肾上腺发育不全，同时缺乏DZ和FZ/XZ。最后，常染色体隐性遗传性肾上腺皮质发育不良(ACD)小鼠的表型与人类小型成人先天性肾上腺发育不良非常相似，缺乏XZ/FZ，具有功能障碍的DZ。目前的工作已经解决了依赖SF-I和DAX-1的肾上腺皮质生长和类固醇生成的调节在体内利用单纯和联合的SF-1和DAX-1缺乏的小鼠模型。此外，应用SF-1半缺陷小鼠的肾上腺代偿性生长模型来评价SF-1在肾上腺皮质增殖中的潜在作用。更多的努力旨在定位克隆ACD基因，这是基于ACD基因是肾上腺发育级联的关键组成部分的假设。
The formation of the adrenal cortex in humans is notable for the presence of two discrete zones, the fetal zone (FZ) which regresses soon after birth and the definitive zone (DZ) which gives rise to the classic steroidogenic zones of the adult cortex. Mice possess an analogous structure to the FZ referred to as the X-zone (YZ) which regresses at puberty in the male and during the first pregnancy in the female. Similar to the human FZ in X-linked Congenital Adrenal Hypoplasia caused by loss of function mutations in DAX-1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita critical region on the X chromosome), the mouse XZ does not regress when DAX-1 is mutated. Only in humans with DAX-1 mutations, however, is the DZ small and hypofunctional. Patients and mice with SF-I mutations have complete adrenal aplasia with absence of both the DZ and FZ/XZ. Lastly, the phenotype of the Autosomal Recessive Adrenocortical Dysplasia (acd) mouse is strikingly similar to human Miniature Adult Congenital Adrenal Hypoplasia, lacking an XZ/FZ and possessing a dysfunctional DZ. Current work has addressed the regulation of SF-I and DAX-1 dependent adrenocortical growth and steroidogenesis in vivo utilizing mouse models of simple and combined SF-1 and DAX-1 deficiency. In addition, the model of compensatory adrenal growth in SF-1 haplo-insufficient mice has been applied to evaluate the potential role of SF-1 in adrenocortical proliferation. Additional efforts aim to positionally clone the acd gene, predicated on the hypothesis that it is a critical component of the adrenal developmental cascade.