title: Inhibitory effects of flavonoids on the reduction of progesterone to 20alpha-hydroxyprogesterone in rat liver.
abstract: The first aim of this study is to characterize the reduction of progesterone in rat liver. Progesterone was mainly reduced to 20alpha-hydroxyprogesterone in the cytosolic fraction of rat liver. The amount of 20alpha-hydroxyprogesterone formed from progesterone in the cytosolic fraction was significantly larger in the males than in the females and this enzyme reaction proceeded not only in the presence of NADPH, but also in the presence of NADH. Furthermore, we attempted to evaluate the inhibitory effects of 15 flavonoids on the NADPH-dependent reduction of progesterone to 20alpha-hydroxyprogesterone in liver cytosol of male rats. The order of the inhibitory potencies was luteolin>apigenin>quercetin>myricetin=fisetin=kaempferol. Other flavonoids exhibited lower inhibitory potencies. Energy-minimized molecular models demonstrated that a planar benzopyrone ring (A and C rings) with a coplanar phenyl ring (B ring) is a structural characteristic determining the inhibitory effects of flavonoids other than isoflavones.
authors.affiliation: Faculty of Education, Kumamoto University, 2-40-1, Kurokami, Kumamoto 860-8555, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Uchida
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okawara
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Abe
authors.forename: Yorishige
authors.initials: Y
authors.lastname: Imamura
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006908:Hydroxyprogesterones / Q000032:analysis / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D005419:Flavonoids; D006908:Hydroxyprogesterones; D009243:NAD; D011374:Progesterone; D009249:NADP