Tissue-specific induction of 17β-hydroxysteroid dehydrogenase type IV by peroxisome proliferator chemicals is dependent on the peroxisome proliferator-activated receptor α
Tissue-specific induction of 17β-hydroxysteroid dehydrogenase type IV by peroxisome proliferator chemicals is dependent on the peroxisome proliferator-activated receptor α
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DOI：
10.1677/joe.0.1580237
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发表时间：
1998-08-01
影响因子：
4
通讯作者：
Corton, JC
中科院分区：
文献类型：
--
作者：
Fan, LQ;Cattley, RC;Corton, JC
17 β-羟基类固醇脱氢酶（17 β-HSD）蛋白家族调节活性17 β-羟基形式的性类固醇的水平。过氧化物酶体增殖物化学品（PPC）诱导大鼠肝脏中17 β-HSD IV型的表达。为了更普遍地表征PPC油17 β-HSD表达的影响，我们确定（1）PPC暴露是否协同诱导17 β-HSD家族的其它成员的表达，（2）其中17 β-HSD被PPC诱导的组织，PPC对17 β-HSD的诱导是否依赖于过氧化物酶体增殖物激活受体α（PPARalpha），小鼠肝脏中PPC效应的中心介质。PPC处理的大鼠肝脏、肾脏、睾丸或子宫中17 β-HSD I、II和III的mRNA水平没有改变。17 β-HSD IV的mRNA或80 kDa全长蛋白水平在肝脏和肾脏中被强烈诱导，但在肾上腺、棕色脂肪、心脏、睾丸和子宫中未被诱导。在处理大鼠的肝脏和肾脏中，还诱导了66 kDa、56 kDa和32 kDa的额外蛋白质，其与抗17 β-HSD IV抗体反应，并且最有可能是17 β-HSD IV的蛋白水解片段。用PPC处理缺乏PPAR α功能形式的小鼠，证明PPC诱导的17 β-HSD IV mRNA或80 kDa蛋白依赖于肝脏和肾脏中的PPAR α表达。我们的研究结果表明，17 β-HSD IV是由PPC通过一个PPAR α依赖性机制诱导的，并支持暴露于PPC导致性类固醇代谢改变的假设。
The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) family of proteins regulates the levels of the active 17 beta-hydroxy forms of sex steroids. The expression of 17 beta-HSD type IV is induced by peroxisome proliferator chemicals (PPC) in rat liver. In order to characterize more generally the impact of PPC oil 17 beta-HSD expression, we determined (1) if expression of other members of the 17 beta-HSD family was coordinately induced by PPC exposure, (2) the tissues in which 17 beta-HSD was induced by PPC, and (3) whether the induction of 17 beta-HSD by PPC was dependent on the peroxisome proliferator-activated receptor alpha (PPAR alpha), the central mediator of PPC effects in the mouse liver. The mRNA levels of 17 beta-HSD I, II, and III were not altered in the liver, kidney, and testis or uterus of rats treated with PPC. The mRNA or 80 kDa full-length protein levels of 17 beta-HSD IV were strongly induced in liver and kidney, but not induced in adrenals, brown fat, heart, testis, and uterus of rats treated with diverse PPC. In liver and kidneys from treated rats, additional proteins of 66 kDa, 56 kDa, and 32 kDa were also induced which reacted with the anti-17 beta-HSD IV antibodies and were most likely proteolytic fragments of 17 beta-HSD IV. Treatment of mice which lack a functional form of PPAR alpha with PPC, demonstrated that PPC-inducibility of 17 beta-HSD IV mRNA or the 80 kDa protein was dependent on PPAR alpha expression in Liver and kidney. Our results demonstrate that 17 beta-HSD IV is induced by PPC through a PPAR alpha dependent mechanism and support the hypothesis that exposure to PPC leads to alterations in sex steroid metabolism.