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Analysis of in situ estrogen production in human osteoporosis.

人类骨质疏松症中原位雌激素产生的分析。

基本信息

批准号：
08670189
负责人：
SASANO Hironobu
金额：
$ 1.41万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

Peripheral aromatization of androgens exert estrogenic actions in many tissues. Recently in situ production of estrogens by aromatase was detected in human bone and cultured osteoblasts and has been proposed to participate in maintenance of bone mass. We examined aromatase expression by immunohistochemistry and mRNA in situ hybridization in 16 cases of tibia (male 2, female 14,62 (]SY.+-。[) 5.2 year old) and quantified the level of aromatase mRNA in 28 cases of rib, femur and lumbar vertebrae (16 male, 12 female, 58.0 (]SY.+-。[) 11.3 year old) by reverse transcriptase-polymerase chain reaction (RT-PCR) in order to study whether or not and in which cell types aromatase was expressed in human bone tissues. We also studied alternative use of multiple exons 1 of its gene and immunolocalization of type I 17 beta-hydroxysteroid dehydrogenase (HSD), which converts estrone produced by aromatase to estradiol. Strong aromatase immunoreactivity and mRNA hybridization as well as type I 17beta-HSD immunoreactivity were detected in lining cells, osteoblasts, chondrocytes of articular cartilage and adipocytes adjacent to bone trabeculae in all the cases examined. Amounts of aromatase mRNA varied greatly among the subjects (11.25 (]SY.+-。[) 9.77,0.61 to 42.84 attomole/ng total RNA). The amount of aromatase expression was not correlated with age or sex of the subjects but positively correlated with the degree of osteroporotic changes evaluated by radiological findings of lumbar vertebrae. Analysis of multiple exons 1 revealed that 1b or fibroblasts type was predominantly (23/26) utilized as a promoter of aromatase gene expression. These results demonstrated that aromatase is expressed widely in human bone tissue and may play important roles in maintenance of human bone tissue.

雄激素的外周芳构化在许多组织中发挥雌激素作用。最近在人骨和培养的成骨细胞中检测到芳香化酶原位产生雌激素，并被认为参与骨量的维持。我们采用免疫组织化学和mRNA原位杂交技术检测了16例胫骨（男2例，女14例，62例）芳香化酶的表达。[) 5.2岁)，定量测定28例肋骨、股骨和腰椎（男性16例，女性12例，58.0例）的芳香化酶mRNA水平。[) 11.3岁)，通过逆转录聚合酶链反应（RT-PCR）研究芳香化酶在人骨组织中是否表达以及在哪些细胞类型中表达。我们还研究了其基因多外显子1的替代使用和I - 17型β -羟基类固醇脱氢酶（HSD）的免疫定位，该酶可将芳香化酶产生的雌酮转化为雌二醇。所有病例的内层细胞、成骨细胞、关节软骨软骨细胞和骨小梁旁脂肪细胞均检测到较强的芳香酶免疫反应性、mRNA杂交和I型17β - hsd免疫反应性。芳香化酶mRNA的数量在受试者之间差异很大（11.25）。[) 9.77,0.61 ~ 42.84原子摩尔/ng总RNA)。芳香化酶的表达量与受试者的年龄或性别无关，但与腰椎放射学表现评估的骨质疏松程度呈正相关。对多个外显子1的分析显示，1b或成纤维细胞类型主要（23/26）被用作芳香酶基因表达的启动子。这些结果表明，芳香化酶在人体骨组织中广泛表达，并可能在人体骨组织的维持中发挥重要作用。