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Endocrinology Vol. 140, No. 7 3334-3341
Copyright © 1999 by The Endocrine Society

ARTICLES

Characterization of Molecular and Catalytic Properties of Intact and Truncated Human 17ß-Hydroxysteroid Dehydrogenase Type 2 Enzymes: Intracellular Localization of the Wild-Type Enzyme in the Endoplasmic Reticulum1

T. J. Puranen, R. M. Kurkela, J. T. Lakkakorpi, M. H. Poutanen2, P. V. Itäranta, J. P. J. Melis, D. Ghosh, R. K. Vihko and P. T. Vihko

Biocenter Oulu and World Health Organization Collaborating Centre for Research on Reproductive Health (T.J.P., R.M.K., M.H.P., P.V.I., J.P.J.M., R.K.V., P.T.V.) and the Department of Anatomy (J.T.L.), University of Oulu, FIN-90220 Oulu, Finland; the Hauptman-Woodward Medical Research Institute, Inc., and Roswell Park Cancer Institute (D.G.), Buffalo, New York 14203; and the Department of Biosciences, Division of Biochemistry (P.T.V.), FIN-00014 University of Helsinki, Finland

Address all correspondence and requests for reprints to: Prof. Pirkko Vihko, Biocenter Oulu and World Health Organization Collaborating Centre for Research on Reproductive Health, University of Oulu, Kajaanintie 50, FIN-90220 Oulu, Finland. E-mail: pvihko{at}whoccr.oulu.fi

Human 17ß-hydroxysteroid dehydrogenase (17HSD) type 2 is a widely distributed enzyme that primarily converts the highly active 17ß-hydroxysteroids to their inactive keto forms. In the present study, full-length human 17HSD type 2 was localized in the endoplasmic reticulum using a double immunofluorescence labeling technique. As a consequence of its strong membrane interaction, full-length human 17HSD type 2 could not be solubilized as a biologically active form in vitro. However, by deleting the first 29 amino acids from the N-terminus, we were able to purify a catalytically active enzyme from the cytosolic fraction of Sf9 insect cells. Biochemical and catalytic properties of the purified truncated human 17HSD type 2 protein confirm its suitability for structure-function analyses of the enzyme. Both intact and truncated 17HSD type 2 enzymes efficiently catalyzed the oxidation of estradiol, testosterone, dihydrotestosterone, androstenediol, and 20{alpha}-dihydroprogesterone. The oxidation of estradiol brought about by human 17HSD type 2 was effectively inhibited by several other steroidal compounds, such as 2-hydroxyestradiol, 5ß-androstan-3{alpha},17ß-diol, 5{alpha}-androstan-3{alpha},17ß-diol, and 5{alpha}-androstan-3ß,17ß-diol. The broad substrate specificity of human 17HSD type 2 together with its predominant oxidative activity and intracellular location, as observed in this study, indicate the physiological role of the enzyme to be primarily an inactivator of highly active 17ß-hydroxysteroids.




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