Characterization of Ke 6, a new 17β-hydroxysteroid dehydrogenase, and its expression in gonadal tissues
Characterization of Ke 6, a new 17β-hydroxysteroid dehydrogenase, and its expression in gonadal tissues
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DOI：
10.1074/jbc.273.35.22664
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发表时间：
1998-08-28
影响因子：
4.8
通讯作者：
Aziz, N
中科院分区：
文献类型：
--
作者：
Fomitcheva, J;Baker, ME;Aziz, N
Ke 6基因的异常调节与小鼠隐性多囊肾病的发展有关。在这份报告中，我们已经表明，Ke 6是一个17 β-羟基类固醇脱氢酶，可以调节生物活性雌激素和雄激素的浓度。Ke 6酶优先是氧化酶，并使雌二醇、睾酮和二氢睾酮失活。然而，该酶具有一定的还原活性，可以从雌酮合成雌二醇。我们发现Ke 6基因在卵巢和睾丸中表达。Ke 6蛋白在卵母细胞周围的卵丘细胞内的存在使其处于控制卵子暴露的类固醇水平的战略位置。以前，已经表明糖皮质激素可以诱导新生啮齿动物肾囊肿，只有在出生后肾脏发育的狭窄时间窗内给予时。我们认为，在cpk，jck和pcy小鼠中发生的Ke 6酶水平的降低可能导致局部性类固醇水平的异常升高，其直接或间接地通过糖皮质激素代谢异常导致隐性肾囊肿病，一种肾脏发育障碍。
The abnormal regulation of the Ke 6 gene has been linked to the development of recessive polycystic kidney disease in the mouse. In this report, we have shown that Ke 6 is a 17 beta-hydroxysteroid dehydrogenase and can regulate the concentration of biologically active estrogens and androgens. The Ke 6 enzyme is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. We find that the Ke 6 gene is expressed within the ovaries and testes. The presence of Ke 6 protein within the cumulus cells surrounding the oocyte places it in a strategic location to control the level of steroids to which the egg is exposed. Previously, it had been shown that glucocorticoids can induce renal cysts in the neonatal rodent, only when given at a narrow time window of postnatal kidney development. We propose that the reduction in the level of Ke 6 enzyme, which occurs in the cpk, jck, and pcy mice, may lead to abnormal elevations in local level of sex steroids, which either directly or indirectly via abnormal glucocorticoid metabolism result in recessive renal cystic disease, a developmental disorder of the kidney.