Cloning of rat 17 beta-hydroxysteroid dehydrogenase type 2 and characterization of tissue distribution and catalytic activity of rat type 1 and type 2 enzymes.

Cloning of rat 17 beta-hydroxysteroid dehydrogenase type 2 and characterization of tissue distribution and catalytic activity of rat type 1 and type 2 enzymes.
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大鼠 17 β-羟基类固醇脱氢酶 2 型的克隆以及大鼠 1 型和 2 型酶的组织分布和催化活性的表征。

DOI:
10.1210/endo.137.5.8612487
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发表时间:
1996
期刊:
影响因子:
4.8
通讯作者:
R. Vihko
R. Vihko
中科院分区:
医学2区
文献类型:
--
作者:
L. Akinola;M. Poutanen;R. Vihko

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17-羟基类固醇脱氢酶(17HSDs)是催化17-羟基和17-酮类固醇之间转化的酶。雌激素和雄激素在17 -羟基形式中都具有最高的活性,因此这些酶调节性激素的生物活性。在这项研究中,我们鉴定了大鼠17HSD 2型的互补DNA (cDNA)。该cDNA编码的蛋白质预计分子量为42,010 Da。该蛋白与人类17HSD 2型酶具有77%的相似性和62%的一致性。此外,两种酶的亲水性也非常相似。这两种同工酶含有一个假定的靠近n端的跨膜区域。然而,大鼠同工酶缺乏人类17HSD 2型的N端和c端存在的两个富含赖氨酸的氨基酸簇。大鼠17HSD 1型和2型酶的组织分布与人的酶非常相似。17HSD 2型在胎盘中表达最高。此外,该酶的1.5千碱基信使RNA在小肠、肝脏和两性肾脏中都被检测到。大鼠17HSD 1型的两个信使rna(1.4和1.7千碱基)仅在卵巢中高表达,在两性的肾脏中浓度极低。瞬时表达的大鼠17HSD 2型几乎只在培养的人胚胎肾293细胞中表现出氧化活性,将雌二醇转化为雌酮,将睾酮转化为雄烯二酮,而大鼠1型酶则相反。数据表明,与相应的人类同种异构体相似,大鼠17HSD 2型主要参与17 β -羟基类固醇在外周组织中氧化为相对不活跃的酮衍生物,而大鼠17HSD 1型主要参与雌二醇的腺体生物合成。
17 beta-Hydroxysteroid dehydrogenases (17HSDs) are enzymes catalyzing the conversion between 17 beta-hydroxy- and 17-ketosteroids. Both estrogens and androgens possess their highest activity in the 17 beta-hydroxy form, and the enzymes, therefore, regulate the biological activity of sex hormones. In this study, we have characterized the complementary DNA (cDNA) for rat 17HSD type 2. The cDNA encodes a protein with a predicted mol wt of 42,010 Da. The protein has 77% similarity and 62% identity with the human 17HSD type 2 enzyme. Furthermore, the hydropathicity profiles of the enzymes are very similar. The two isozymes contain a putative transmembrane region close to the N-terminus. However, the rat isozyme lacks the two lysine-rich amino acid cluster present at the N- and C-terminals of human 17HSD type 2. The tissue distribution of the rat 17HSD type 1 and type 2 enzymes is very similar to that of the human enzymes. The highest expression of 17HSD type 2 was detected in the placenta. In addition, a 1.5-kilobase messenger RNA for the enzyme was detected in the small intestine, liver, and kidney of both sexes. The two messenger RNAs for rat 17HSD type 1 (1.4 and 1.7 kilobases) were highly expressed only in the ovary, and at very low concentrations in the kidney of both sexes. Transiently expressed rat 17HSD type 2 showed oxidative activity almost exclusively in cultured human embryonic kidney 293 cells, converting estradiol into estrone and testosterone into androstenedione, whereas the opposite was observed for the rat type 1 enzyme. The data suggest that similarly to the corresponding human isoforms, rat 17HSD type 2 is mostly involved in the oxidation of 17 beta-hydroxysteroids into their relatively inactive keto derivative in peripheral tissues, whereas rat 17HSD type 1 is mainly involved in the glandular biosynthesis of estradiol.
DOI: 10.1002/j.1460-2075.1990.tb07513.x
发表时间: 1990-10-01
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
JACKSON, MR;NILSSON, T;PETERSON, PA
通讯作者: PETERSON, PA
DOI: 10.1021/bi00018a001
发表时间: 1995-05-09
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
JORNVALL, H;PERSSON, B;GHOSH, D
通讯作者: GHOSH, D
大鼠胎盘中 P450(17α) 和 P450SCC 基因的表达和调控。
DOI: 10.1210/endo.130.3.1537294
发表时间: 1992
期刊: Endocrinology
影响因子: 4.8
作者:
Durkee,TJ;McLean,MP;Hales,DB;Payne,AH;Waterman,MR;Khan,I;Gibori,G
通讯作者: Gibori,G
位于染色体17cen----q25上的雌激素17-酮类固醇还原酶基因的调控。
DOI: --
发表时间: 1989
期刊: The Journal of biological chemistry
影响因子: --
作者:
Tremblay,Y;Ringler,GE;Morel,Y;Mohandas,TK;Labrie,F;Strauss3rd,JF;Miller,WL
通讯作者: Miller,WL
大鼠胎盘分泌雄激素。
DOI: 10.1210/endo-119-6-2642
发表时间: 1986
期刊: Endocrinology
影响因子: 4.8
作者:
Warshaw,ML;Johnson,DC;Khan,I;Eckstein,B;Gibori,G
通讯作者: Gibori,G