17p-hydroxysteroid

The 17P-hydroxysteroid oxidoreductase enzymes (HSOR) occur as two distinct isoforms (I and II). They are involved in the conversion of estrone to estradiol. The type I enzyme converts estrone to estradiol (also androstenedione to testosterone) and the type II catalyses the reverse reaction. Phytoestrogens have been shown to inhibit both HSOR enzymes in vitro. 

Peltoketo H, Nokelainen P, Palo YS, Vihko R, Vihko P (1999) Two 17P-hydroxysteroid dehydrogenases (17HSDs) of estriadol biosynthesis 17HSD type 1 and type 7. J Steroid Biochem Mol Biol, 69(1-6) 431-439. 

Figure 6b shows the modeled a helix F interface in human 17P-hydroxysteroid dehydrogenase type 2. Alanine-237 is 3 A from the hydrophobic part of the side chain of methionine-241 on the other subunit. Methionine-241 is 3.2 A from serine-234. Alanine-230 is 3.7 A from phenylalanine-242 and 4.5 A from valine-245. Alanine-238, the other anchoring residue, is 4.1 A from alanine-238 on the other subunit. 

Brooks, J.D. and Thompson, L.U. 2005. Mammalian lignans and genistein decrease the activities of aromatase and 17p-hydroxysteroid dehydrogenase in MCF-7 cells. J. Steroid Biochem. Mol. Biol. 94, 461—467. 

Another anti-cancer mechanism of isoflavones may involve inhibition of key enzymes of estrogen metabolism, such as 3 p-hydroxy steroid dehydrogenase, 17P-hydroxysteroid dehydrogenase, 5a-reductase and aromatase, as a consequence of which the level of active steroid hormones is affected [81, 106, 107],... 

Schuster, D., Nashev, L.G., Kirchmair, J., Laggner, C., Wolber, G., Langer, T., and Odermatt, A. (2008) Discovery of nonsteroidal 17P-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compormd libraries. Journal of Medicinal Chemistry, 51, 4188—4199. 

After being orally administered 100 mg/kg of an alcohol extract of Phyllanthus amarus daily for 30 days, female mice were unable to become pregnant. On withdrawal of Phyllanthus amarus for 45 days, mice were successfully mated. Reductions in 3 3- and 17p-hydroxysteroid dehydrogenase (HSD) levels were noted as probably affecting hormonal conversions in the ovaries (Rao and Alice 2001). 

A polyphenol-rich fraction of pomegranate seed oil inhibited 17p-hydroxysteroid dehydrogenase type 1 at concentrations ranging from 100 to 1000 pg/ml. The oil also inhibited proliferation of estrogen receptor (ER)-positive human breast cancer cells (MCF-7), inhibited invasion of MGF-7 across a membrane, and induced apoptosis in ER-negative human breast cancer cells (MDA-MB-435) (Kim et al. 2002). An older study indicated that dried pomegranate seed contains the compound estrone at a concentration of 17 mg/kg (Heftmann et al. 1966) a more recent analysis indicated that no estrone was present (Choi et al. 2006). 

Khan N, Sharma KK, Andersson S, Auehus RJ (2004) Human 17p-hydroxysteroid dehydrogenases types 1, 2, and 3 catalyze bi-directional equilibrium reactions, rather than unidirectional metabolism, in HEK-293 cells. Arch Bioehem Biophys 429 50-59... 

FIGURE 11.54 Libraries of type 3 17 3-hydroxysteroid dehydrogenase inhibitors. (From Maltais, R., Luu-The, V., and Poirier, D., Parallel solid-phase synthesis of 3 3-peptido-3 -hydroxy-5 -androstan-17-one derivatives for inhibition of type 3 17P-hydroxysteroid dehydrogenase, Bioorg. Med. Chem., 9, 3101, 2001 Maltais, R., Luu-The, V., and Poirier, D., Synthesis and optimization of a new family of type 17P-hydroxysteroid dehydrogenase inhibitors by parallel liquid phase chemistry, J. Med. Chem., 45, 640, 2002.)... 

Baker, M.E. (1995) Biochem. J., 309, 1029-1030, Enoyl-acyl-carrier-protein reductase and Mycobacterium tuberculosis InhA do not conserve the Tyr-Xaa-Xaa-Xaa-Lys motif in mammalian 1 lp and 17P hydroxysteroid dehydrogenases and Drosophila alcohol dehydrcgenase. 

Bail, J, Laroche,T, Marre-Foumier, F and Habrioux, G (1998) Aromatase and 17P-hydroxysteroid dehydrogenase inhibition by flavonoids. Cancer Lett., 133, 101-106. 

Androstenedione is the most important precursor hormone of androgens in females. Plasma levels are often increased in hirsute women. Next to 17a-hydroxy-progesterone, it is an important diagnostic parameter of 21-hydroxylase deficiency in plasma and amniotic fluid [52], A decreased ratio between testosterone and androstenedione is indicative of 17P-hydroxysteroid dehydrogenase deficiency. The first mass-spectrometrically determined concentrations of plasma an-... 

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