17beta-Hydroxysteroid dehydrogenase/
17-ketosteroid reductases (17HSD/KSR) play a key role in regulating
steroid receptor occupancy in normal tissues and
tumors. Although 17HSD/KSR activity has been detected in ovarian epithelial
tumors, our understanding of which
isoforms are present and their potential for
steroid metabolism is limited. In this investigation, 17HSD/KSR activity from a series of ovarian epithelial
tumors was assayed in cytosol and microsomes under conditions which differentiate between
isoforms. Inhibition studies were used to further characterize the
steroid specificities of
isoforms in the two subcellular fractions. Activity varied widely between
tumors of the same histopathologic classification. The highest levels of activity were observed in mucinous
tumors. Michaelis constants, maximum velocities,
estradiol-17beta/
testosterone (E(2)/T) activity ratios and inhibition patterns were consistent with a predominance of microsomal 17HSD/KSR2 and cytosolic 17HSD/KSR5,
isoforms reactive with both E(2) and T, with evidence of estrogenic 17HSD/KSR1 in cytosol from some samples. In
tumors where activity and
mRNA expression were both characterized, Northern blots, PCR and sequence analysis indicated 17HSD/KSR5 was the predominant
isoform. The presence of 17HSD/KSR5, which also has both 3alpha-HSD/KSR and 20alphaHSD/KSR activity, and 17HSD/KSR2 which also has 20alpha-HSD activity, could influence not only
estrogen and
androgen binding but
progesterone receptor occupancy, as well, in receptor-containing
tumors.