Hydroxylated metabolites of tamoxifen are formed in vivo and bound to estrogen receptor in target tissues.

摘要: After in vivo administration of [3H]tamoxifen to immature female rats and chickens, polar metabolites tamoxifen were found plasma, liver, uterus, oviduct. 4-Hydroxytamoxifen M2, another hydroxylated metabolite tamoxifen, the major tritiated compounds cytosol KCl-nuclear extract target tissues appeared occupy estrogen receptor sites since their accumulation these fractions was saturable, resistant charcoal, prevented by estradiol. In rat 4-hydroxytamoxifen predominant during 24 h following injection, then its concentration declined while M2 became predominant. also chicken oviduct where is acting as a full antagonist. Moreover, oviduct, lamb uterus able convert into vitro. Other tissues, such dimethylbenz (a) anthracene-induced mammary tumors, MCF7 cells, did not transform significantly. formed vitro bind selectively with high affinity low dissociation rate similar These results demonstrate that retained on due affinity. Since we have separately shown anti-estrogen, more potent than itself conclude mostly indirectly via metabolite(s).