Possible Involvement of Aromatase Overexpression Induced by Cyclo-Oxygenase-2 in the Pathogenesis of Idiopathic Gynecomastia

Abstract

The pathogenesis of idiopathic gynecomastia, which shows no imbalance in serum estrogens and androgens levels unlike gynecomastia of other causes, is unknown. It seems to be of interest to study the in situ aromatase expression in idiopathic gynecomastia to investigate a possible involvement of intratumoral biosynthesis of estrogens in the pathogenesis of this disease. The expression level of aromatase mRNA was studied by a real-time polymerase chain reaction (PCR) assay in four idiopathic gynecomastia cases (two florid type and two fibrous type). In addition, the proportion of promoter usage (promoters I.3, I.4, l.7, and PII) of the aromatase gene was determined by PCR-gel electrophoresis. Localization of aromatase and cyclo-oxygenase-2 (COX-2) expression was studied by immunohistochemistry. The aromatase mRNA level of the florid-type gynecomastia (3.05 and 1.66) was higher than that in the fibrous type (0.76 and 0.04). The proportion of promoter Pll in the florid type (94.1% and 84.8%) was very high as compared with that of the fibrous type (0.7% and 0.5%). Immunohistochemical studies have revealed that aromatase and COX-2 were strongly expressed in the duct epithelial cells in the florid type, but they were weak or negative in the fibrous type. COX-2 is suggested to upregulate aromatase expression by enhancing the transcription via promoter Pll in idiopathic gynecomastia of the florid type but not of the fibrous type. Because idiopathic gynecomastia initially develops as the florid type and regresses as the fibrous type, a high estrogen milieu induced by increased aromatase expression is speculated to play some role in the pathogenesis of idiopathic gynecomastia.

Key words:

• Aromatase
• COX-2
• Gynecomastia
• Promoter

ACKNOWLEDGMENTS

This study was supported in part by a Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labour and Welfare, Japan.

Notes

3. Harada, N, Utsumi, TTakagi, Y. Molecular and epidemiological analyses of abnormal expression of aromatase in breast cancer Pharmacogenetics 1995; (5)Spec No S59–64.