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，并已提出参与骨量的维持。我们通过免疫组织化学和mRNA原位杂交方法检测了16例胫骨（男性2例，女性14例，62例（]SY. ±-.））中芳香酶的表达。28例（男16例，女12例，58.0 ± 0.05）肋骨、股骨和腰椎中芳香化酶mRNA的表达水平。[）11.3岁），以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的多个外显子1的替代使用和I型17 β-羟基类固醇脱氢酶（HSD）的免疫定位，该脱氢酶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、关节软骨的软骨细胞和骨小梁附近的脂肪细胞均检测到强芳香化酶免疫反应和mRNA杂交以及I型17 β-HSD免疫反应。芳香化酶mRNA的量在受试者之间差异很大（11.25 ± 0.001）。（9.77，0.61 ~ 42.84阿托摩尔/ng总RNA）。芳香化酶的表达量与受试者的年龄或性别无关，但与腰椎放射学检查结果评估的骨质疏松变化程度呈正相关。多个外显子1的分析表明，1b或成纤维细胞型主要（23/26）被用作芳香化酶基因表达的启动子。这些结果表明芳香化酶在人骨组织中广泛表达，可能在人骨组织的维护中起重要作用。

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.