Characterization of 17 beta-hydroxysteroid dehydrogenase activity and mRNA 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 (E2) and estrone (E1) 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 Km values of 2.4, 0.4, 14.7, and 2.0 microM for E2, E1, 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.
Carsol
J L
JL
Laboratoire de Cancérologie Expérimentale, INSERM CJF 93-II, Institut Jean Roche, Faculté de Médecine Secteur Nord, Marseille, France.
Martin
P M
PM
de Launoit
Y
Y
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D015342:DNA Probes; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008577:Meningeal Neoplasms / Q000201:enzymology*; D008579:Meningioma / Q000201:enzymology*; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D013347:Subcellular Fractions / Q000201:enzymology
D015342:DNA Probes; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases