Moreau François, Mittre Hervé, Benhaim Annie, Bois Camille, Bertherat Jérome, Carreau Serge, Reznik Yves
INRA USC 2006, Caen, France.
Eur J Endocrinol. 2009 Jan;160(1):93-9. doi: 10.1530/EJE-08-0215. Epub 2008 Oct 30.
The aromatase enzyme catalyzes the final stage of estrogen biosynthesis pathway from androgens. Its expression in the adrenal is poorly studied except for the rare estrogen-producing adrenocortical tumors. In order to further characterize aromatase expression in the adrenal, we evaluated the aromatase enzyme activity, Cyp19a1 gene expression level, and promoter utilization in normal adrenal tissues and in adrenocortical secreting tumors.
Six normal adult adrenals (NA), 2 feminizing adrenal tumors (FT), 10 cortisol-producing adenomas with overt (CS, n=4) or sub-clinical Cushing syndrome (SCS, n=6) and 3 aldosterone-producing adenomas (APA) were studied. Tissue aromatase activity was determined by the tritiated ((3)H)-water method. Total aromatase mRNA were measured by a competitive RT-PCR. Promoter regions PII and PI.4-derived transcripts were also studied in NA, FT, and other steroid-producing tumors by a semi-quantitative comparative RT-PCR. Immunofluorescence analysis was performed in normal human adrenal tissues.
Aromatase activity was detected in NA tissues and in all tumor subtypes, at high levels in both FT. In NA, aromatase immunofluorescence was detected in the cytoplasm of steroidogenic cells, mainly from zona reticularis. Compared with NA, aromatase transcript levels were similar in CS and APA, lower in SCS and similar or higher in FT. Promoter analysis suggested predominant PII utilization in NA, APA, and SCS, but similar PII and PI.4 utilization in CS tumors.
Aromatase is expressed at similar levels in normal adrenal and in adrenocortical tumors, but at variably high levels in FT. Different promoter utilization patterns are found among tumor subtypes.
芳香化酶催化雄激素生成雌激素生物合成途径的最后阶段。除了罕见的产生雌激素的肾上腺皮质肿瘤外，其在肾上腺中的表达研究较少。为了进一步明确芳香化酶在肾上腺中的表达特征，我们评估了正常肾上腺组织和肾上腺皮质分泌肿瘤中的芳香化酶活性、Cyp19a1基因表达水平及启动子利用情况。
研究了6个正常成人肾上腺（NA）、2个女性化肾上腺肿瘤（FT）、10个伴有明显库欣综合征（CS，n = 4）或亚临床库欣综合征（SCS，n = 6）的皮质醇分泌腺瘤以及3个醛固酮分泌腺瘤（APA）。采用氚化（³H）水法测定组织芳香化酶活性。通过竞争性逆转录聚合酶链反应（RT-PCR）检测总芳香化酶信使核糖核酸（mRNA）。还通过半定量比较RT-PCR研究了正常肾上腺、女性化肾上腺肿瘤及其他类固醇生成肿瘤中启动子区域PII和PI.4衍生转录本。对正常人类肾上腺组织进行免疫荧光分析。
在正常肾上腺组织和所有肿瘤亚型中均检测到芳香化酶活性，在两个女性化肾上腺肿瘤中活性均较高。在正常肾上腺中，芳香化酶免疫荧光在类固醇生成细胞的细胞质中检测到，主要来自网状带。与正常肾上腺相比，皮质醇分泌腺瘤和醛固酮分泌腺瘤中的芳香化酶转录水平相似，亚临床库欣综合征中的水平较低，女性化肾上腺肿瘤中的水平相似或更高。启动子分析表明，正常肾上腺、醛固酮分泌腺瘤和亚临床库欣综合征中主要利用启动子PII，但皮质醇分泌腺瘤中启动子PII和PI.4的利用相似。
芳香化酶在正常肾上腺和肾上腺皮质肿瘤中的表达水平相似，但在女性化肾上腺肿瘤中表达水平较高。在肿瘤亚型中发现了不同的启动子利用模式。
