男性乳房肥大症乳腺组织内芳香化酶的表达及其发病机制的探讨
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摘要
近年来,男性乳房肥大症(GYN)的发病率逐年上升,治疗主要通过外科手术方法,但多数患者对于手术治疗仍具恐惧心理,而且术后胸部疤痕增生严重影响着美观及生活质量。GYN其确切发病机理尚不明确,其中以生理性多见,多数患者伴血清学雌激素水平升高。故有学者考虑其发病原因与男性乳房局部雌激素水平过度表达相关。芳香化酶是雌激素生物合成的关键酶,其与男性乳房肥大症局部组织内雌激素分泌协同性关系尚无明确定论,但在芳香化酶转基因雄性小鼠中表现乳房肥大,由此不难考虑人类男性乳房肥大症的发病与局部芳香化酶过度表达所致局部雌激素水平过高间可能存在一定相关性。
作为雌激素生物合成关键酶—芳香化酶在GYN组织局部的表达及与其发病间的相关性研究在国内外尚未报道。本研究主要通过检测GYN组织内芳香化酶(aromatase,AROM)的表达及其mRNA的转录情况。了解芳香化酶在GYN发病中的可能作用。本组研究对象为2008年9月至2009年1月期间就诊于我院的、并经临床检查、手术切除及病理学检查明确诊断为GYN患者。检测乳腺组织内及血清雌二醇(E2)与睾酮(T)水平,比较组织内E2/T比值与血清E2/T比值间差异性、免疫组化法检测GYN乳腺组织中芳香化酶及雌激素受体(ER)、Rt-PCR法扩增GYN乳腺组织内CYP19-mRNA。结果显示:9例GYN患者中8例ER(+),1例ER(-);4例AROM(+),5例AROM(-);乳腺组织内CYP19-mRNA转录8例(+),1例(-);乳腺组织E2/T比值与血清E2/T比值间具有显著性差异。说明:1、男性乳房肥大症的发生不仅与血清E2水平增高相关,且与乳腺组织内E2水平有关,尤其是与E2/T比例失调相关;2、GYN乳腺组织中证实有AROM和调节其编码的单基因CYP19mRNA的存在,间接证明乳腺组织中AROM的存在是乳腺组织局部E2明显增高导致E2、T比例失调的原因,致使乳腺导管上皮细胞增生,男性乳房发育;3、芳香化酶在GYN乳腺组织中的表达,及其在GYN发病中的作用为GYN病人应用芳香化酶抑制剂治疗提供依据。
1.Objective and significance:
In recent years, the incidence of the gynecomastia(GYN) is increasing, but the pathogenisis of the disease is still not clear. The major method of the treatment of the GYN is the operation. Most authorities think GYN is caused by the increased level E2 in local breast tissue. Aromatase is the key enzyme in the catalyzing androgens into estrogen, and play important role in the estrogen synthesis. There are still no reports about the correlation between the aromatase expression with the estrogen level change in the local breast tissue, especially with the E2/T ratio change in the local breast tissue. With my study, I want to do something in this field, to find out the correlation between the GYN pathogenesis with the aromatase in the local breast tissue.
2.Material , Methods and Results
Materials: The study is aimed at the nine patients who had the pain lump in the front chest wall, and diagnosed to gynecomastia in our hospital from Sept. 2008 to Jan.2009. Methods: Compare the variability between the local E2/T ratio and the serum E2/T ratio; detect the aromatase and ER in the breast tissue via IHC method; dectect the CYP19-mRNA in the the breast tissue via Rt-PCR. Results: In 9 patients, 8 patients are ER(+),1 is ER(-); 4 patients are AROM(+) , 5 are AROM( - ) ; 8 patients are CYP19-mRNA(+) , 1 is CYP19-mRNA (-);and the variation between the the local E2/T ratio and the serum E2/T ratio is significance(p<0.01)
3.Conclusions
The GYN is one kind of sex hormone dependent disease, and the rise of the serum E2 is the whole-body etiologic factor of GYN, and the change of E2/T ratio in the breast tissue by the aromatse is an an important local etiologic factor of GYN
作为雌激素生物合成关键酶—芳香化酶在GYN组织局部的表达及与其发病间的相关性研究在国内外尚未报道。本研究主要通过检测GYN组织内芳香化酶(aromatase,AROM)的表达及其mRNA的转录情况。了解芳香化酶在GYN发病中的可能作用。本组研究对象为2008年9月至2009年1月期间就诊于我院的、并经临床检查、手术切除及病理学检查明确诊断为GYN患者。检测乳腺组织内及血清雌二醇(E2)与睾酮(T)水平,比较组织内E2/T比值与血清E2/T比值间差异性、免疫组化法检测GYN乳腺组织中芳香化酶及雌激素受体(ER)、Rt-PCR法扩增GYN乳腺组织内CYP19-mRNA。结果显示:9例GYN患者中8例ER(+),1例ER(-);4例AROM(+),5例AROM(-);乳腺组织内CYP19-mRNA转录8例(+),1例(-);乳腺组织E2/T比值与血清E2/T比值间具有显著性差异。说明:1、男性乳房肥大症的发生不仅与血清E2水平增高相关,且与乳腺组织内E2水平有关,尤其是与E2/T比例失调相关;2、GYN乳腺组织中证实有AROM和调节其编码的单基因CYP19mRNA的存在,间接证明乳腺组织中AROM的存在是乳腺组织局部E2明显增高导致E2、T比例失调的原因,致使乳腺导管上皮细胞增生,男性乳房发育;3、芳香化酶在GYN乳腺组织中的表达,及其在GYN发病中的作用为GYN病人应用芳香化酶抑制剂治疗提供依据。
1.Objective and significance:
In recent years, the incidence of the gynecomastia(GYN) is increasing, but the pathogenisis of the disease is still not clear. The major method of the treatment of the GYN is the operation. Most authorities think GYN is caused by the increased level E2 in local breast tissue. Aromatase is the key enzyme in the catalyzing androgens into estrogen, and play important role in the estrogen synthesis. There are still no reports about the correlation between the aromatase expression with the estrogen level change in the local breast tissue, especially with the E2/T ratio change in the local breast tissue. With my study, I want to do something in this field, to find out the correlation between the GYN pathogenesis with the aromatase in the local breast tissue.
2.Material , Methods and Results
Materials: The study is aimed at the nine patients who had the pain lump in the front chest wall, and diagnosed to gynecomastia in our hospital from Sept. 2008 to Jan.2009. Methods: Compare the variability between the local E2/T ratio and the serum E2/T ratio; detect the aromatase and ER in the breast tissue via IHC method; dectect the CYP19-mRNA in the the breast tissue via Rt-PCR. Results: In 9 patients, 8 patients are ER(+),1 is ER(-); 4 patients are AROM(+) , 5 are AROM( - ) ; 8 patients are CYP19-mRNA(+) , 1 is CYP19-mRNA (-);and the variation between the the local E2/T ratio and the serum E2/T ratio is significance(p<0.01)
3.Conclusions
The GYN is one kind of sex hormone dependent disease, and the rise of the serum E2 is the whole-body etiologic factor of GYN, and the change of E2/T ratio in the breast tissue by the aromatse is an an important local etiologic factor of GYN
引文
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