CHARACTERIZATION OF 17-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY AND MESSENGER-RNA ABUNDANCE IN HUMAN MENINGIOMA TUMORS

Meningioma benign tumors possess significant levels of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity. Two different 17 beta-HSDs have been cloned and characterized. The cytosolic 17 beta-HSD I which exclusively catalyzes the interconversion of 17 beta-estradiol (E(2)) and estrone (E(1)) preferentially uses NADP(+) and NADPH as cofactors. In contrast, the mitochondrial-microsomal 17 beta-HSD II catalyzes both the estrogenic as well as the androgenic substrates of the 17 beta-HSD and uses NAD(+) and NADH as cofactors. We demonstrated here that the 17 beta-HSD activity in meningioma tissue homogenate is both estrogenic and androgenic with K-m values of 2.4, 0.4, 14.7, and 2.0 mu M for E(2), E(1), testosterone (T), and Delta 4-androstenedione (Delta 4), respectively. NAD(+)-NADH is almost exclusively used as cofactor in this tissue. Moreover, fractionation of meningioma tissue revealed that most of the 17 beta-HSD activity is present in the mitochondrial-microsomal fraction. Although Northern blot analysis on meningiomas with a specific probe for human 17 beta-HSD I showed no band, the specific cDNA probe of human 17 beta-HSD II hybridized at the expected size of 1.5 kb, which was also present in placenta. On four different meningioma tumors, we were able to correlate 17 beta-HSD II mRNA expression to high levels of 17 beta-HSD activity. Taken together, the present data suggest that the meningioma 17 beta-HSD could be the 17 beta-HSD II.