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

Meningioma benign tumors possess significant levels of 17 beta-hydroxy steroid dehydrogenase (17 beta-HSD) activity. Two different 17 beta-HS Ds have been cloned and characterized. The cytosolic 17 beta-HSD I whi ch exclusively catalyzes the interconversion of 17 beta-estradiol (E(2 )) and estrone (E(1)) preferentially uses NADP(+) and NADPH as cofacto rs. In contrast, the mitochondrial-microsomal 17 beta-HSD II catalyzes both the estrogenic as well as the androgenic substrates of the 17 be ta-HSD and uses NAD(+) and NADH as cofactors. We demonstrated here tha t the 17 beta-HSD activity in meningioma tissue homogenate is both est rogenic 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 i n this tissue. Moreover, fractionation of meningioma tissue revealed t hat most of the 17 beta-HSD activity is present in the mitochondrial-m icrosomal fraction. Although Northern blot analysis on meningiomas wit h a specific probe for human 17 beta-HSD I showed no band, the specifi c cDNA probe of human 17 beta-HSD II hybridized at the expected size o f 1.5 kb, which was also present in placenta. On four different mening ioma tumors, we were able to correlate 17 beta-HSD II mRNA expression to high levels of 17 beta-HSD activity. Taken together, the present da ta suggest that the meningioma 17 beta-HSD could be the 17 beta-HSD II .