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Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme AKC1C1Brožič, Petra ...Phytoestrogens are plant-derived, non-steroidal constituents of our diets. They can act as agonists or antagonists of estrogen receptors, and they can modulate the activities of the key enzymes in ... estrogen biosynthesis. Much lessis known about their actions on the androgen and progesterone metabolizingenzymes. We have examined the inhibitory action of phytoestrogens on the key human progesterone-metabolizing enzyme, 20alphahydroxysteroid dehydrogenase (AKR1C1 ). This enzyme inactivates progesterone and the neuroactive 3alpha,5alpha-tetrahydroprogesterone, to form their less active counterparts, 20alpha-hydroxyprogesterone and 5alpha-pregnane-3alpha,20alpha-diol, respectively. We overexpressed recombinant human AKR1Cl in Escherichia coli, purified it to homogeneity, and examined the selected phytoestrogens as inhibitors of NADPH-dependent reduction of a common AKR substrate, 9,10-phenantrenequinone and progesterone.The most potent inhibitors were 7-hydroxyflavone, 3,7-dihydroxyflavone and flavanone naringenin with 1C50 values in the low microM range. Docking of the flavones in the active site of AKR1C1 revealed their possible binding modes, in which they are sandwiched between the Leu308 and Trp227 of AKR1Cl .Source: Molecular and cellular endocrinology. - ISSN 0303-7207 (Letn. 259, 2006, str. 30-42)Type of material - article, component partPublish date - 2006Language - englishCOBISS.SI-ID - 21449689
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Brožič, Petra | 27575 |
Šmuc, Tina, 1980- | 25593 |
Gobec, Stanislav, 1970- | 15284 |
Lanišnik-Rižner, Tea | 11699 |
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