【作者】 王永慧；

【导师】 曾正陪；

【作者基本信息】 北京协和医学院 ， 内分泌与代谢， 2011， 博士

【摘要】 目的：原发性醛固酮增多症(原醛症,PA)是一组醛固酮分泌增多,肾素-血管紧张素系统受抑制但不受钠负荷调节的疾病。原醛症发病机制的分子水平研究国外仅有少许报道。Ras相关的C3肉毒素底物1(Ras-related C3 botulinum toxinsubstrate 1, Rac1)本身是一个癌基因,近年研究发现Rac1的过度表达可以显著增强醛固酮介导的盐皮质激素受体(MR)转录活性。但目前尚未见至刂Rac1与原醛症相关的报道。本研究采用RT-PCR的方法检测]Rac1、盐皮质激素受体mRNA在原醛症(醛固酮分泌瘤、特发性醛固酮增多症)及库欣综合征(皮质醇分泌瘤、非ACTH依赖性肾上腺皮质大结节增生症、库欣病及异位ACTH综合征引起的肾上腺增生)以及正常肾上腺皮质中的表达,初步探讨Rac1基因、盐皮质激素受体mRNA的表达在肾上腺皮质疾病中的作用。方法：1、提取正常肾上腺皮质(n=6),原醛症(n=19)包括醛固酮分泌瘤(APA, n=15)和特发性醛固酮增多症(IHA,n=4),库欣综合征(CS,n=22)包括肾上腺皮质醇分泌瘤(CPA,n=10)、非ACTH依赖性肾上腺皮质大结节增生症(AIMAH,n=7)、库欣病及异位ACTH综合征引起的肾上腺增生(n=3)、异位ACTH综合征肺类癌(n=2)组织的总RNA；2、RT-PCR方法检测上述不同组织中Rac1基因、盐皮质激素受体和内参照β-actin mRNA的表达；3、比较Rac1基因、盐皮质激素受体mRNA在上述不同组织中的表达差异,并与原醛症及库欣综合征患者的临床资料行相关性分析。结果：1、Racl基因mRNA在原醛症及库欣综合征肾上腺组织和肿瘤中的表达1)原醛症和库欣综合征中功能性肾上腺皮质腺瘤及肾上腺增生组织中Racl基因mRNA的表达均高于正常肾上腺皮质,差异有显著统计学意义(均p<0.01),但原醛症与库欣综合征组间差异无统计学意义(p>0.05)；2)原醛症中醛固酮分泌瘤组Racl基因mRNA的表达高于特发性醛固酮增多症组,差异有显著统计学意义(p<0.01)：特发性醛固酮增多症组Rac1基因mRNA的表达有高于正常肾上腺皮质的趋势,但差异无统计学意义(p>0.05)3)库欣综合征中皮质醇分泌瘤和肾上腺皮质增生组Racl基因mRNA的表达均高于正常肾上腺组织,差异有显著统计学意义(均p<0.01)；不同病因的库欣综合征间Racl基因mRNA的表达差异无统计学意义(p>0.05)；4)醛固酮分泌瘤组Racl基因mRNA的表达高于库欣综合征中肾上腺皮质增生组,差异有统计学意义(p<0.05)；5)2例异位ACTH综合征的肺类癌中表达分别为0.9和0.93。2、盐皮质激素受体mRNA在原醛症及库欣综合征肾上腺组织和肿瘤中的表达1)原醛症和库欣综合征中功能性肾上腺皮质腺瘤及肾上腺增生组织中盐皮质激素受体mRNA的表达高于正常肾上腺皮质,差异有显著统计学意义(p<0.01),库欣综合征组盐皮质激素受体mRNA的表达高于原醛症组,差异有显著统计学意义(p<0.01)：2)原醛症中特发性醛固酮增多症组盐皮质激素受体mRNA的表达有高于正常肾上腺皮质的趋势,但差异无统计学意义(p<0.05)；特发性醛固酮增多症组与醛固酮分泌瘤组盐皮质激素受体mRNA的表达差异无统计学意义(p<0.05)。3)库欣综合征中皮质醇分泌瘤和肾上腺增生组盐皮质激素受体mRNA的表达均高于正常肾上腺组织,差异有显著统计学意义(均p<0.01),肾上腺增生组中盐皮质激素受体nRNA的表达高于皮质醇分泌瘤组,差异有显著统计学意义(p<0.01)4)2例异位ACTH综合征的肺类癌中表达分别为0.85和0.37。3、Racl基因、盐皮质激素受体mRNA的表达与原醛症及库欣综合征的临床相关性1)原醛症Rac1基因及盐皮质激素受体mRNA的表达与临床资料均不相关(均p>0.05)。2)库欣综合征a.Rac1基因mRNA的表达与HOMA-IR呈正相关(r=0.588,p=0.034),与血糖曲线下面积呈正相关(r=0.547,p=0.035)；b.盐皮质激素受体mRNA的表达与0点血皮质醇呈正相关(r=0.641,p=0.025)。结论：1、Rac1基因及盐皮质激素受体mRNA在正常肾上腺皮质有表达,在原醛症、库欣综合征中的表达均高于正常肾上腺皮质组织,提示Rac1基因及盐皮质激素受体与原醛症、库欣综合征的发生可能相关；2、库欣综合征中Rac1基因mRNA的表达与HOMA-IR、血糖曲线下面积呈正相关,证实了胰岛素抵抗增加Rac1基因mRNA的表达；盐皮质激素受体mRNA的表达与0点血皮质醇呈正相关,证实了高皮质醇血症促进盐皮质激素受体mRNA的表达。目的：第一部分研究从mRNA水平上显示Rac1基因、盐皮质激素受体在正常肾上腺皮质及原醛症、库欣综合征中的表达存在差异,故本部分研究拟观察Rac1、盐皮质激素受体蛋白在正常肾上腺皮质及原醛症、库欣综合征中的表达,进一步从蛋白水平探讨Rac1、盐皮质激素受体在肾上腺皮质疾病中的作用,并分析与mRNA表达水平上的异同。方法：1、提取正常肾上腺皮质(n=6),原醛症(n=19)包括醛固酮分泌瘤(APA, n=15)和特发性醛固酮增多症(IHA, n=4),库欣综合征(CS,n=22)包括肾上腺皮质醇分泌瘤(CPA, n=10)、非ACTH依赖性肾上腺皮质大结节增生症(AIMAH, n=7)库欣病及异位ACTH综合征引起的肾上腺增生(n=3)、异位ACTH综合征肺类癌(n=2)组织的总蛋白,并测定蛋白浓度。2、Western blot方法检测上述不同组织中Rac1、盐皮质激素受体和内参β-actin蛋白的表达；分析目的条带和内参照条带的灰度比值,对Rac1、盐皮质激素受体蛋白的表达进行半定量分析。3、比较上述不同组织中Rac1、盐皮质激素受体蛋白表达的差异。并对Rac1、盐皮质激素受体蛋白在不同肾上腺皮质疾病中的表达水平与相应患者的临床资料行相关性分析,并分析与mRNA表达水平上的异同。结果：1、Rac1蛋白在原醛症及库欣综合征患者肾上腺组织和肿瘤中的表达1)原醛症和库欣综合征中功能性肾上腺皮质腺瘤及肾上腺增生组织中Rac1蛋白的表达均高于正常肾上腺皮质,差异有统计学意义(p<0.01,p<0.05),原醛症组Rac1蛋白的表达高于库欣综合征组,差异有统计学意义(p<0.05)2)原醛症中醛固酮分泌瘤及特发性醛固酮增多症组中Rac1蛋白的表达均高于正常肾上腺皮质,差异有显著统计学意义(均p<0.01)。醛固酮分泌瘤与特发性醛固酮增多症组Rac1蛋白的表差异无统计学意义(p>0.05)；3)库欣综合征中皮质醇分泌瘤组Rac1蛋白的表达高于正常肾上腺组织(p<0.01),肾上腺增生组Rac1蛋白的表差有高于正常肾上腺皮质的趋势,但差异无统计学意义(p>0.05),皮质醇分泌瘤组和肾上腺增生组Rac1蛋白的表达差异无统计学意义(p>0.05)；4)2例异位ACTH综合征的肺类癌中表达(分别为0.75和0.94)。2、盐皮质激素受体蛋白在原醛症及库欣综合征患者肾上腺组织和肿瘤中的表达1)原醛症中功能性肾上腺皮质腺瘤及肾上腺增生组织中盐皮质激素受体蛋白的表达高于正常肾上腺皮质,差异有显著统计学意义(p<0.01),原醛症组盐皮质激素受体蛋白的表达高于库欣综合征组,差异有显著统计学意义(p<0.01),库欣综合征组盐皮质激素受体蛋白的表达有高于正常肾上腺皮质的趋势,但差异无统计学意义(p>0.05)；2)原醛症中特发性醛固酮增多症组及醛固酮分泌瘤组盐皮质激素受体蛋白的表达均高于正常肾上腺皮质,差异有显著统计学意义(均p<0.01),特发性醛固酮增多症组与醛固酮分泌瘤组盐皮质激素受体蛋白的表达差异无统计学意义(p>0.05)；3)库欣综合征中皮质醇分泌瘤组盐皮质激素受体的蛋白表达高于正常肾上腺皮质组织,差异有显著统计学意义(p<0.01),皮质醇分泌瘤组盐皮质激素受体蛋白的表达高于肾上腺皮质增生组,差异有统计学意义(p<0.05),肾上腺皮质增生组盐皮质激素受体蛋白的表达与正常肾上腺皮质相比,差异无统计学意义(p>0.05)；4)2例异位ACTH综合征的肺类癌中表达(分别为1.22和0.30)。3、Rac1、盐皮质激素受体蛋白的表达呈正相关,差异有显著统计学意义(p<0.01)。4、Rac1、盐皮质激素受体蛋白的表达与原醛症及库欣综合征患者的临床相关性1)原醛症a.原醛症患者中Rac1蛋白的表达与病程中最高舒张压呈正相关(r=0.471,p=0.042),与近期收缩压呈正相关(r=0.543,p=0.016),与立位醛固酮增加值呈正相关(r=0.583,p=0.018)；b.原醛症患者中盐皮质激素受体蛋白的表达与24小时尿钠呈负相关(r=-0.610,p=0.027)；c.将原醛症患者分为血管紧张素II有反应组(n=7)和无反应组(n=12),血管紧张素II有反应组Racl、盐皮质激素受体蛋白的表达高于无反应组,差异有显著统计学意义(均p<0.01)；d.将原醛症患者按HOMA-IR>2.69为胰岛素抵抗组(n=4), HOMA-IR≤2.69为非胰岛素抵抗组(n=7),盐皮质激素受体蛋白的表达在胰岛素抵抗组高于非胰岛素抵抗组,差异有统计学意义(p<0.05)；e.将原醛症患者按24小时尿钠≥200mmol为高尿钠组(n=8),24小时尿钠<200为正常尿钠组(n=5),高尿钠组盐皮质激素受体蛋白的表达低于正常尿钠组,差异有统计学意义(p<0.05)；f.将原醛症患者按近期血压控制在收缩压≥140mmHg和(或)舒张压≥90mmHg为血压未控制达标组(n=12),血压<140/90mmHg为血压控制达标组(n=7),血压未控制达标组Racl蛋白表达高于血压控制达标组,差异有统计学意义(p<0.05)。2)库欣综合征a.库欣综合征中Racl蛋白的表达与血钾呈负相关(r=0.564,p=0.010)；b.库欣综合征中盐皮质激素受体蛋白的表达与24小时尿钠呈负相关(r=0.697,p=0.017),与肾上腺瘤或手术切除肾上腺的体积呈负相关(r=0.652,p=0.002),与肾上腺瘤或手术切除肾上腺的重量呈负相关(r=0.722,p=0.000)；c.将库欣综合征患者按是否合并胰岛素抵抗、尿钠水平、血压水平分亚组,亚组间Rac1、MR蛋白的表达差异无统计学意义(均p>0.05)。结论：1、从蛋白水平也证实,在原发性醛固酮增多症及皮质醇分泌瘤表达高于正常肾上腺皮质,提示Racl基因及盐皮质激素受体与原醛症、皮质醇分泌瘤的发生可能相关；2、原醛症中Racl蛋白的表达与立位血醛固酮水平的变化、血压呈正相关,血管紧张素II有反应组Racl蛋白的表达高于无反应组,血压未控制达标组Racl蛋白的表达高于血压控制达标组,提示血醛固酮水平的变化、高血压是引起Racl蛋白表达升高的因素；3、原醛症中盐皮质激素受体蛋白的表达与24小时尿钠呈负相关,高尿钠组盐皮质激素受体蛋白的表达低于正常尿钠组,提示高尿钠不能抑制盐皮质激素受体蛋白的表达；血管紧张素II有反应组盐皮质激素受体蛋白的表达高于无反应组,胰岛素抵抗组盐皮质激素受体蛋白的表达高于非胰岛素抵抗组,提示血醛固酮水平的变化、胰岛素抵抗是引起盐皮质激素受体蛋白表达升高的因素；4、Racl蛋白的表达与盐皮质激素受体蛋白的表达一致,提示Racl的活化增加了盐皮质激素受体蛋白的表达。5、库欣综合征中肾上腺增生组盐皮质激素受体mRNA的表达增加,但蛋白表达不高,提示盐皮质激素受体在翻译水平上受其他因素调控。6、在库欣综合征中盐皮质激素受体蛋白的表达与肾上腺瘤或手术切除肾上腺的体积、重量呈负相关,提示盐皮质激素受体蛋白的表达可能影响肾上腺皮质的生长。更多还原

【Abstract】 Objectives:Primary aldosteronism (PA) is a group of disorders in which aldosterone production is inappropriately high, relatively autonomous from the renin-angiotensin system, and nonsuppressible by sodium loading. Studies on the genetic pathogenesis of primary aldosteronism is rare in foreign report. Rac1(Ras-related C3 botulinum toxinsubstrate 1) is a kind of oncogene, in recent years, some researches testified that overexpression of active Rac1 significantly potentiated aldosterone-induced mineralocorticoid receptor transcriptional activity. But, we didn’t find any researches about primary aldosteronism with active Rac1.This study aims to analyze the mRNA expression level of Racl and mineralocorticoid recepto in adrenal tissues with patients of primary aldosteronism (including aldosterone-producing adenomas, idiopathic hyperaldosteronism) and cushing syndrome(including cortisol producing adenomas, ACTH-independent macronodular adrenal hyperplasia, cushing disease, and ectopic ACTH syndrome).Methods:1. Total RNA was extracted from 6 normal human adrenal cortex,19 primary aldosteronism include 15 adrenal aldoterone-producing adenomas(APA) and 4 idiopathic hyperaldosteronism(IHA),22 cushing syndrome include 10 cortisol-producing adenomas(CPA),7 ACTH-independent macronodular adrenal hyperplasia (AIMAH),2 cushing disease,3 ectopic ACTH syndrome and and then the total RNA was reverse transcripted to cDNA;2. RT-PCR was used to analyze the mRNA expression level of Rac1 and mineralocorticoid recepto in different tissues. The expression levels of the target genes were relatively quantified using (3-actin as internal control;3. The expression levels of the target genes were compared in different tissues. It was studied whether the mRNA expression of Racl and mineralocorticoid receptor correlated with clinical data in different adrenocortical disease.Results:1. Racl mRNA expression in adrenal tumors or adrenal tissues of primary aldosteronism and cushing syndrome patients:1) Expression in primary aldosteronism and cushing syndrome were significant higher than that in normal adrenal cortex(all, p<0.01). There was no statistical significance between primary aldosteronism and cushing syndrome(p>0.05);2) Expression in aldosterone-producing adenoma was significant higher than that in idiopathic hyperaldosteronism (p<0.01);3) Expression in cortisol-producing adenoma and adrenal hyperplasia were significant higher than that in normal adrenal cortex(all, p<0.01). There was no statistical significance between cortisol-producing adenoma and adrenal hyperplasia(p>0.05);4) Expression in aldosterone-producing adenoma was higher than that in adrenal hyperplasia caused by cushing disease and ectopic ACTH syndrome (p<0.05);5) Expressed in lung carcinoid tumor tissue of 2 ectopic ACTH syndrome cases (0.9 and 0.93, respectively).2. Mineralocorticoid receptor mRNA expression in adrenal tumors or adrenal tissues of primary aldosteronism and cushing syndrome patients:1)Expression in primary aldosteronism and cushing syndrome were significant higher than that in normal adrenal cortex(all, p<0.01), expression in cushing syndrome was significance higher than that in primary aldosteronism (p<0.01);2)Expression in idiopathic hyperaldosteronism tended to be higher than that in normal adrenal cortex, but the difference showed no statistical significance(p>0.05). There was no statistical significance between idiopathic hyperaldosteronism and aldosterone-producing adenoma(p>0.05);3)Expression in cortisol-producing adenoma and adrenal hyperplasia were significant higher than that in normal adrenal cortex(all, p<0.01), expression in adrenal hyperplasia was statistically significant higher than that in cortisol-producing adenoma(p<0.01).4) Expressed in lung carcinoid tumor tissue of 2 ectopic ACTH syndrome cases (0.85 and 0.37, respectively).3. The correlation between Racl, mineralocorticoid receptor mRNA expression and the clinical manifestations of primary aldosteronism and cushing syndrome patients:1) Primary aldosteronism Racl and mineralocorticoid receptor mRNA expression were not related to clinical manifestations(all, p>0.05);2) Cushing syndromea)Racl mRNA expression was positively related to HOMA-IR (r=0.588, p =0.034), and positively related to area under glucose curve (r=0.547, p =0.035);b) Mineralocorticoid receptor mRNA expression was positively related to serum cortisol at 0 AM(r=0.641,p=0.025).Conclusion:1. Racl and mineralocorticoid receptor mRNA expressed in normal adrenal cortex, Racl and mineralocorticoid receptor mRNA expression level in primary aldosteronism and cushing syndrome were significant higher than that in normal adrenal cortex, which indicated that they might have tight correlation with adrenocortical disease(primary aldosteronism and cushing syndrome);2. Racl mRNA expression in cushing syndrome was positively related to HOMA-IR and area under glucose curve, which indicated that insulin resistance might improve Racl mRNA expression. Mineralocorticoid receptor mRNA expression in cushing syndrome was related to serum cortisol, which indicated that high serum cortisol improve mineralocorticoid receptor mRNA expression. Objectives:The purpose of this study is to detect the protein level of Rac1 and mineralocorticoid receptor in human different adrenocortical diseases, including primary aldosteronism, cushing syndrome and normal adrenal cortex, to investigate the relationship of Rac1 and mineralocorticoid receptor with adrenocortical diseases.Methods:1. Total protein was extracted from 6 normal human adrenal cortex,19 primary aldosteronism include 15 adrenal aldoterone-producing adenomas(APA) and 4 idiopathic hyperaldosteronism(IHA),22 cushing syndrome include 10 cortisol-producing adenomas(CPA),7 ACTH-independent macronodular adrenal hyperplasia (AIMAH),2 cushing disease,3 ectopic ACTH syndrome, and then, The concentration of protein was evaluated by the means of Bicinchoninic acid.2. Using western blot we analyzed the protein expression of Rac1,MR and P-actin. The protein expression of Racl and MR was semi-quantified by dividing the grayness value of Rac1/β-actin and MR/β-actin in the same sample and compared among the different tissues.3. It was studied whether the protein expression of Racl and MR correlated with clinical data in different adrenocortical diseases, and the difference between mRNA and protein expression of Rac1 and MR were also compared.Results:1. Racl protein expression in adrenal tumors or adrenal tissues of Primary aldosteronism and Cushing syndrome patients:1) Racl protein expression in primary aldosteronism and cushing syndrome werehigher than that in normal adrenal cortex (p<0.01, p<0.05), expression in primary aldosteronism was higher than that in cushing syndrome (p<0.05);2) Racl protein expression in aldosterone-producing adenoma and idiopathic hyperaldosteronism were significant higher than that in normaladrenal cortex(all, p<0.01). There was no statistical significance when compared with aldosterone-producing adenoma group and idiopathic hyperaldosteronism group(p>0.05);3) Racl protein expression in cortisol-producing adenoma was significant higher than that in normal adrenal cortex(p<0.01). There was no statistically significant difference between adrenal hyperplasia and normal adrenal cortex(p>0.05). There was no statistical significance between cortisol-producing adenoma and adrenal hyperplasia(p>0.05);4) Racl protein expressed in lung carcinoid tumor tissue of 2 ectopic ACTH syndrome cases (0.75 and 0.94 respectively).2. Mineralocorticoid receptor protein expression in adrenal tumors or adrenal tissues of primary aldosteronism and Cushing syndrome patients:1) Mineralocorticoid receptor protein expression in primary aldosteronism was significant higher than that in normal adrenal cortex(p<0.01). Mineralocorticoid receptor protein expression in primary aldosteronism was significant higher than that in cushing syndrome(p<0.01). There was no statistical significance when compared cushing syndrome with normal adrenal cortex(p>0.05);2) Mineralocorticoid receptor protein expression in aldosterone-producing adenoma and idiopathic hyperaldosteronism were significant higher than that in normal adrenal cortex (all, p<0.01), but was no statistical significance when compared aldosterone-producing adenoma with idiopathic hyperaldosteronism;3) Mineralocorticoid receptor protein expression in cortisol-producing adenoma was significant higher than that in normal adrenal cortex(p<0.01). Mineralocorticoid receptor protein expression in cortisol-producing adenoma was significant higher than that in adrenal hyperplasia(p<0.05). There was no statistically significant difference between adrenal hyperplasia and normal adrenal cortex(p>0.05); 4) MR protein expressed in lung carcinoid tumor tissue of 2 ectopic ACTH syndrome cases(1.22 and 0.30 respectively).3. Rac1 protein expression in all adrenocortical diseases patients was positively related to mineralocorticoid receptor protein expression.4. The correlation between Rac1, mineralocorticoid receptor protein expression and the clinical manifestations of Primary aldosteronism and Cushing syndrome patients.1) Primary aldosteronisma)Racl protein expression was positively related to highest diastolic blood pressure in the course(r=0.543,p=0.016), positively related to recently systolic blood pressure (r=0.583,p=0.018), and positively related to the increase of plasma aldosterone level to upright stimulation(r=0.583,p=0.018);b) Mineralocorticoid receptor protein expression was negatively related to 24 hours urine sodium(r=-0.610, p=0.027);c)The protien levels of Rac1 and mineralocorticoid receptor in angiotensin-responsive primary aldosteronism were significant higher than that in angiotensin-unresponsive primary aldosteronism(all,p<0.01);d) The protien levels of mineralocorticoid receptor in primary aldosteronism with insulin resistance was higher than that in without insulin resistance(p<0.05);e) The protien levels of mineralocorticoid receptor in primary aldosteronism with high urine sodium was significant lower than that in mormal urine sodium (p <0.05); f) The protien levels of Rac1 in primary aldosteronism with bad control of blood pressure was significant higher than that in good control of blood pressure (p <0.05). 2) Cushing syndromea) Rac1 protein expression was negatively related to 24 hours urine sodium(r=-0.564, p=0.010);b) Mineralocorticoid receptor protein expression was negatively related to 24 hours urine sodium(r=-0.697, p=0.017), negatively related to tumor or adrenal weight(r=-0.652,p=0.002), negatively related to tumor or adrenal adrenal volume(r=-0.722,p=0.000);c) The protien levels of Racl and mineralocorticoid receptor protein expression were no statistical significance between with insulin resistance and without insulin resistance, high urine sodium and mormal urine sodium, bad control of blood pressure and good control of blood pressure(all,p>0.05).Concliusion:1. It is tested in protein level that Racl, mineralocorticoid receptor protein expression level in primary aldosteronism and cushing syndrome were significant higher than that in normal adrenal cortex, which indicated that they might have tight correlation with adrenocortical disease(primary aldosteronism and cushing syndrome);2. In primary aldosteronism patient, Rac1 protein expression was positively related to the increase of plasma aldosterone level to upright stimulation and blood pressure; The protien levels of Rac1 in angiotensin-responsive primary aldosteronism was higher than that in angiotensin-unresponsive primary aldosteronism, the protien levels of Rac1 in bad control of blood pressure was higher than that in good control of blood pressure, which indicated that the increase of plasma aldosterone level to upright stimulation and high blood pressure might improve Racl protein expression;3. In primary aldosteronism patient, mineralocorticoid receptor protein expression was negatively related to 24 hours urine sodium, the protien levels of mineralocorticoid receptor in high urine sodium was lower than that in mormal urine sodium, which indicated that the increase of urine sodium couldn’t suppress mineralocorticoid receptor protein expression; the protien levels of mineralocorticoid receptor in angiotensin-responsive primary aldosteronism was higher than that in angiotensin-unresponsive primary aldosteronism, in with insulin resistance was higher than that in without insulin resistance, which indicated that the increase of plasma aldosterone level to upright stimulation and insulin resistance might improve mineralocorticoid receptor protein expression; 4. Racl protein expression was positively related to mineralocorticoid receptor protein expression, which indicated that activated Rac1 might improve mineralocorticoid receptor protein expression;5. In cushing syndrome, the mRNA levels of mineralocorticoid receptor was high in adrenal hyperplasia, but the protein levels of mineralocorticoid receptor wasn’t high, which indicated that some other factors modify MR protein translation;6. In cushing syndrome, mineralocorticoid receptor protein expression was negatively related to tumor or adrenal weight and volume, which indicated that mineralocorticoid receptor protein expression might relate with the growth of adrenal cortex.更多还原