Analysis of in situ estrogen production in human osteoporosis.

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，并被认为参与了骨量的维持。应用免疫组织化学和原位杂交技术检测了16例(男2例，女14例，62(-))胫骨组织中芳香化酶的表达。[5.2岁])，并对28例(男16例，女12例，女58.0例)肋骨、股骨和腰椎的芳香酶基因表达水平进行了定量检测。[)11.3岁)，以研究人骨组织中是否表达芳香化酶以及在哪些细胞类型中表达芳香化酶。我们还研究了其基因多个外显子1的替代使用和I型17β-羟基类固醇脱氢酶(HSD)的免疫定位，HSD将芳香酶产生的雌酮转化为雌二醇。所有病例的衬里细胞、成骨细胞、关节软骨细胞和邻近骨小梁的脂肪细胞均有较强的芳香酶免疫反应、mRNA杂交和I型17β-HSD免疫反应。芳香酶mRNA的量在受试者之间差异很大(11.25(]sy.+-)。[]9.77，0.61至42.84 attomole/ng总RNA)。芳香酶的表达与受试者的年龄、性别无关，但与腰椎X线表现所评价的骨质疏松程度呈正相关。对多个外显子1的分析表明，1b或成纤维细胞类型是芳香酶基因表达的主要启动子(23/26)。这些结果表明，芳香化酶在人骨组织中广泛表达，并可能在人骨组织的维持中发挥重要作用。

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.