3-BETA-HYDROXYSTEROID DEHYDROGENASE ISOMERASE IN THE FETAL ZONE AND NEOCORTEX OF THE HUMAN FETAL ADRENAL-GLAND
3-BETA-HYDROXYSTEROID DEHYDROGENASE ISOMERASE IN THE FETAL ZONE AND NEOCORTEX OF THE HUMAN FETAL ADRENAL-GLAND
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DOI：
10.1210/endo-126-5-2487
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发表时间：
1990-05-01
期刊：
影响因子：
4.8
通讯作者：
MASON, JI
中科院分区：
文献类型：
--
作者：
DOODY, KM;CARR, BR;MASON, JI
确定人胎儿肾上腺（HFA）的胎儿区具有减少的3 β =羟基类固醇脱氢酶/Δ 4 -5异构酶2（β HSD）活性与新皮层或定形区相比，但是，3 β HSD活性可以通过用ACTH处理在原代细胞培养物中诱导。因此，具有两个不同的类固醇生成区的HFA提供了研究该酶的调节的极好模型，所述两个不同的类固醇生成区具有3 β HSD活性的差异以及响应ACTH而增加3 β HSD活性的能力。使用抗纯化的人胎盘微粒体3 β HSD的多克隆抗体检测HFA的胎儿和新皮质区中3 β HSD的存在。将HFA的胎儿和新皮质区的匀浆在十二烷基硫酸钠-聚丙烯酰胺凝胶上进行电泳并进行免疫印迹后，仅在新皮质区中证实了分子大小为45 kDa的3 β HSD蛋白的存在。胎儿和新皮质区外植体培养物的ACTH处理（>2天）产生与免疫可检测的3 β HSD蛋白各自水平相关的皮质醇分泌增加。皮质醇和硫酸脱氢表雄酮分别是新皮质和胎儿区外植体的主要类固醇产品。在ACTH处理后，免疫可检测的3 β HSD在新皮质中被诱导到更大的程度。这些发现提供了在胎儿区缺乏3 β HSD活性的证据，以前认为这是内源性抑制剂存在的结果，是由于在腺体的这一部分缺乏蛋白质。HFA胎儿区中3 β HSD表达的缺乏或最小可能是由于调节3 β HSD合成的组织特异性因子的作用（或缺乏）。
The fetal zone of the human fetal adrenal (HFA) gland is established to have decreased 3.beta.=hydroxysteroid dehydrogenase/.DELTA.4-5 isomerase 2(.beta.HSD) activity compared to the neocortex or definitive zone, 3.beta.HSD activity, however, can be induced in primary cell culture through treatment with ACTH. Therefore, the HFA with two distinct steroidogenic zones with differences in 3.beta.HSD activity as well as the capacity to increase 3.beta.HSD activity in response to ACTH provides an excellent model to study the regulation of this enzyme. The presence of 3.beta.HSD in the fetal and neocortex zones of the HFA was examined using a polyclonal antibody raised against purified human placental microsomal 3.beta.HSD. After homogenates of the fetal and neocortical zones of the HFA were electrophoresed on a sodium dodecyl sulfate-polyacrylamide gel and immunoblotted, the presence of the 3.beta.HSD protein with a molecular size of 45 kDa could be demonstrated only in the neocortical zone. ACTH treatment (>2 days) of fetal and neocortical zone explant cultures produced increases in cortisol secretion associated with the respective levels of immunodetectable 3.beta.HSD protein. Cortisol and dehydroepiandrosterone sulfate were the respective principal steroid products of neocortical and fetal zone explants. After ACTH treatment, immunodetectable 3.beta.HSD was induced to a greater magnitude in the neocortex. These findings provide evidence that the lack of 3.beta.HSD activity in the fetal zone, previously considered to be the result of the presence of an endogenous inhibitor is due to an absence of the protein in this portion of the gland. The lack or minimal expression of 3.beta.HSD in the fetal zone of HFA may be due to the action (or lack thereof) of a tissue-specific factor regulating the synthesis of 3.beta.HSD.