17-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY CORRELATES WITH THE TYPE-2 17-BETA-HYDROXYSTEROID DEHYDROGENASE MESSENGER-RNA ABUNDANCE IN HUMAN MENINGIOMA TUMORS

Benign meningioma tumors possess significant levels of 17 beta-hydroxy steroid dehydrogenase (17 beta-HSD) activity. Two different 17 beta-HS Ds were discovered in human placenta: one highly estrogen specific and using NADP(+)/NADPH as cofactors (type-1 17 beta-HSD), and a second o ne that utilizes both androgens and estrogens as substrates with NAD()/NADH (type-2 17 beta-HSD). Recently, two further human 17 beta-HSDs were isolated. A testis-specific 17 beta-HSD (type-3 17 beta-HSD) favo rs the reduction of Delta(4)-androstenedione to testosterone, and a ub iquitously expressed type-4 17 beta-HSD preferentially catalyzes the o xidation of estradiol and Delta(5)-androstenediol. In this study we ch aracterize the expression levels of different types of 17 beta-HSD in a wide series of tumors. Using the Northern blotting method we show th at type-1, -3, and -4 17 beta-HSDs are not detectable in meningiomas. In contrast, the type-2 17 beta-HSD RNA is present in 6 of 17 meningio mas and its abundance is directly correlated with estrogenic 17 beta-H SD activity (r(2) = 0.74). The presence of type-2 17 beta-HSD is also demonstrated by in situ hybridization. RT-PCR acid Western blots show that type-4 17 beta-HSD is also present, though at much lower levels. The progesterone receptor level, the epidermal growth factor receptor level, and the age of the patients are not correlated with the estroge nic 17 beta-HSD activity or type-2 17 beta-HSD mRNA expression level.