AROMATASE IN HUMAN BONE TISSUE

Peripheral aromatization of androgens exert estrogenic actions in many tissues, Recently in situ production of estrogens by aromatase,vas de tected in human bone and cultured osteoblasts and has been proposed to participate in the maintenance of bone mass. We examined aromatase ex pression by immunohistochemistry and mRNA in situ hybridization in 16 cases of tibia (female 2 male, 14 female, 62 +/- 5.2 years old) and qu antified the level of aromatase mRNA in 28 cases of rib, femur, and lu mbar vertebrae (16 male, 12 female, 58.0 +/- 11.3 years old) by revers e transcriptase-polymerase chain reaction (RT-PCR) in order to study w hether 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 dehyd rogenase (HSD), which converts estrone produced by aromatase to estrad iol. Strong aromatase immunoreactivity and mRNA hybridization as well as type I 17 beta-HSD immunoreactivity were detected in lining cells, osteoblasts, chondrocytes of articular cartilage, and adipocytes adjac ent to bone trabeculae in all the cases examined. Amounts of aromatase mRNA varied greatly among the subjects (11.25 +/- 9.77, 0.61 +/- 42.8 4 attomol/ng of total RNA). The amount of aromatase expression was not correlated with age or gender of the subjects but positively correlat ed with the degree of osteroporotic changes evaluated by radiological findings of lumbar vertebrae. Analysis of multiple exons 1 revealed th at 1b or fibroblast type was predominantly (23/26) utilized as a promo ter of aromatase gene expression. These results demonstrated that arom atase is expressed widely in human bone tissue and may play important roles in maintenance of human bone tissue.