17 beta-Hydroxysteroid dehydrogenases/17-ketosteroid reductases (17HSDs) modulate the biological activity
of certain estrogens and androgens by catalyzing reductase or dehydrogenase reactions between 17-keto- and 17 beta-hydroxysteroids.
General function
Metabolism, Enzyme, Oxidoreductase
Comment
Nokelainen P et al demonstrated expression cloning of a novel type of 17HSD,
chronologically named 17HSD type 7, from the HC11 cell line derived from mouse mammary gland. The
cloned cDNA, 1.7 kb in size, encodes a protein of 334 amino acids with a calculated molecular mass of 37,317
Da. The primary structure contains segments characteristic of enzymes belonging to the short-chain
dehydrogenase/reductase superfamily. Strikingly, mouse 17HSD type 7 (m17HSD7) shows 89% identity with a
recently cloned rat protein called PRL receptor-associated protein (PRAP). The function of PRAP has not yet
been demonstrated. The enzymatic characteristics of m17HSD7 and RT-PCR-cloned rat PRAP (rPRAP) were
analyzed in cultured HEK-293 cells, where both of the enzymes efficiently catalyzed conversion of estrone (E1)
to estradiol (E2). With other substrates tested no detectable 17HSD or 20 alpha-hydroxysteroid dehydrogenase
activities were found. Kinetic parameters for m17HSD7 further indicate that E1 is a preferred substrate for this
enzyme. Relative catalytic efficiencies (Vmax/K(m) values) for E1 and E2 are 244 and 48, respectively.
Cellular localization
Cytoplasmic
Comment
Ovarian function
Steroid metabolism, Luteinization
Comment
Expression regulated by
Comment
Ovarian localization
Luteal cells
Comment
Nokelainen P et al found that 17HSD7 is most abundantly expressed in the ovaries of pregnant animals. Further
studies show that the rat enzyme is primarily expressed in the middle and second half of pregnancy, in parallel
with E2 secretion from the corpus luteum. The
results indicate that 17HSD7 is an enzyme of E2 biosynthesis, which is predominantly expressed in the corpus
luteum of the pregnant animal.