In vitro and in vivo inhibition of nuclear type II estrogen binding sites in the dorsolateral prostate of noble rats.
Competition analyses with a number of known bioflavonoids and related compounds revealed that three of them competed effectively for type II [3H]estradiol- 17 beta ([3H]E2) binding sites (type II sites) in the nuclei of rat dorsolateral prostate (DLP). Amongst the bioflavonoids tested, quercetin was the most effect, exhibiting approx. a 50% inhibition at 3000-fold molar excess concentration. In contrast, rutin and hesperitin were both not effective. Methyl p-hydroxyphenyllactate (MeHPLA), a suspected "endogenous" ligand for uterine type II sites [1; J. Biol. Chem. 263, 1988, 7203-7210], competed as well as estradiol-17 beta (E2) for prostatic type II sites (50% inhibition at 30-fold molar excess), whereas its demethylated product, HPLA, did not. 4,4'Dihydroxybenzylidene acetophenone, an esterase-stable MeHPLA analog, was also found to be a good competitor, exhibiting a 50% inhibition at 100-fold molar excess concentration. In a preliminary in vivo study, quercetin, administered either orally or subcutaneously, was found to be effective in preventing a joint testosterone (T) and E2 treatment-induced elevation of type II sites in rat DLP. Quercetin treatments also caused a small but significant reduction (17-18%) in DLP relative gland weights (gland wt/body wt) in T + E2-treated animals. Taken together, these data suggest that bioflavonoids and related compounds may influence prostatic function via interactions with prostatic type II sites.
Ho
S M
SM
Department of Biology, Tufts University, Medford, MA 02155.
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D000818:Animals; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011794:Quercetin / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D005419:Flavonoids; D007773:Lactates; D004958:Estradiol; C055915:methyl 4-hydroxyphenyllactate; D011794:Quercetin