Steroid 5alpha reductase mRNA type 1 is differentially regulated by androgens and glucocorticoids in the rat liver.
Steroid 5alpha reductase mRNA type 1 is differentially regulated by androgens and glucocorticoids in the rat liver.
复制标题
类固醇 5α 还原酶 1 型 mRNA 受大鼠肝脏中雄激素和糖皮质激素的差异调节。
作者：
M. El;W. El;Lamia El
睾酮和5α-二氢睾酮(DHT)是哺乳动物体内的主要雄性激素(雄激素)。在雄激素依赖的组织中，类固醇5α还原酶催化睾酮(T)转化为具有生物效力的类固醇(DHT)。在大鼠组织中发现了两种5α还原酶同工酶。I型同工酶主要在大鼠肝脏中表达，而雄激素靶组织主要表达同工酶II。研究了雄激素和糖皮质激素对大鼠肝脏中类固醇5α还原酶I型(5alphaR1)信使RNA丰度的影响。肾上腺切除(ADX)后14天，5AlphaR1mRNA的稳态水平显著下降至对照组的1.5%，而地塞米松(Dex)(0.5 mg/100g)可在40h内使5AlphaR1mRNA的表达增加到正常值的两倍。双侧睾丸切除后8天内，大鼠肝脏中5AlphaR1mRNA的表达增加到正常值的1.75倍，而注射睾酮不能降低去势动物肝脏中5AlphaR1mRNA的表达。在原代培养的大鼠肝细胞中加入地塞米松(1微米)，24小时和48小时后，5AlphaR1mRNA的表达分别下降5倍和3倍。然而，DHT(0.5微米)在24和48小时后分别诱导2倍和7倍的5alphaR1mRNA表达。对5alphaR1基因的体外核连续分析表明，无论是在完整的肝细胞还是在培养的肝细胞中，5alphaR1基因的合成速度与其稳定水平之间没有相关性。这些结果似乎表明，糖皮质激素和雄激素对大鼠肝脏中的5alphaR1mRNA有不同的调节作用。此外，我们的发现似乎表明，5alphaR1基因的调节主要是在转录后水平上。
Testosterone and 5alpha-dihydrotestosterone (DHT) are the principal male hormones (androgens) in mammals. The enzyme, steroid 5alpha reductase catalyzes the conversion of testosterone (T) to its biologically potent steroid (DHT) in androgen dependent tissues. Two 5alpha reductase isoenzymes have been identified in rat tissues. The type I isoenzyme has been shown to be predominately expressed in the rat liver, whereas androgen target tissues of the genital tract express mainly isoenzyme II. The effects of androgens and glucocorticoids on the abundance of steroid 5alpha reductase type I (5alphaR1) messenger RNA in the rat liver were examined. Steady state levels of 5alphaR1 mRNA decreased dramatically to 1.5% of control levels 14 days following adrenalectomy (ADX), whereas dexamethasone (Dex) administered (0.5 mg/100 g) to ADX animals enhanced the expression of 5alphaR1 to twice its' normal values within 40 hours. Bilateral orchiectomy induced, within eight days, the expression of 5alphaR1 mRNA in the rat liver to 1.75 fold the normal value while testosterone injection failed to reduce this enhanced expression in castrated animals. Addition of Dex (1 microM) to primary cultures of rat hepatocyte resulted in a five- and three-fold reduction in the mRNA expression of 5alphaR1 after 24 and 48 hours, respectively. DHT (0.5 microM) however, induced the expression of 5alphaR1 mRNA by two- and seven-fold 24 and 48 hours post-treatment, respectively. In vitro nuclear run-on analysis of the 5alphaR1 gene showed no correlation between the rate of synthesis and steady state levels of this mRNA either in the intact liver or in cultured hepatocytes. These results appear to suggest that glucocorticoids and androgens differentially regulate 5alphaR1 mRNA in the rat liver. Moreover, our findings appear to indicate that regulation of 5alphaR1 gene is primarily at the post-transcriptional level.
登录
查看更多内容
糖皮质激素对 DDT1MF-2 细胞系生长和雄激素受体浓度的影响。
DOI：
10.1016/0022-4731(87)90365-7
发表时间：
1987
期刊：
Journal of steroid biochemistry
影响因子：
--
作者：
Syms,AJ;Nag,A;Norris,JS;Smith,RG
通讯作者：
Smith,RG
类固醇 5 α-还原酶 1 中的四个氨基酸片段赋予对竞争性抑制剂非那雄胺的敏感性。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Thigpen,AE;Russell,DW
通讯作者：
Russell,DW
大鼠类固醇 5 α-还原酶同工酶的组织分布和动力学特征。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Normington,K;Russell,DW
通讯作者：
Russell,DW
细胞色素 P-450c 和 P-450d mRNA 在培养的大鼠肝细胞中的表达。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Silver,G;Krauter,KS
通讯作者：
Krauter,KS
糖皮质激素调节大鼠 α1-酸性糖蛋白基因 5 侧翼区域的表达。
DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Klein,ES;Reinke,R;Feigelson,P;Ringold,GM
通讯作者：
Ringold,GM