Effects of antiestrogens on the induction of vitellogenin and its mRNA in Xenopus laevis.
The egg yolk protein precursor vitellogenin is induced by estrogen in the liver of male Xenopus laevis. The large rise in serum vitellogenin is accompanied by a corresponding increase in intracellular levels of vitellogenin and its mRNA. In the present study this model system was used to examine the subcellular sites of action of triphenylethylene antiestrogens (e.g. tamoxifen). Tamoxifen was extensively metabolized to 4-hydroxytamoxifen in Xenopus and both of these antiestrogens were used in this study. Pre-injection with tamoxifen or 4-hydroxytamoxifen suppressed the estrogen-dependent induction of vitellogenin in serum. 4-Hydroxytamoxifen also inhibited the induction of intracellular vitellogenin and its mRNA by estrogen suggesting that this metabolite of tamoxifen is able to inhibit estrogen-induced transcription of the vitellogenin genes. Neither tamoxifen nor 4-hydroxytamoxifen stimulated the production of serum vitellogenin as assayed by a sensitive dot immunoblot assay. However either compound alone induced low amounts of vitellogenin mRNA and stimulated the production of intracellular vitellogenin to levels 10-40% of those produced by similar doses of estradiol. Since 10-40% of the serum levels of vitellogenin produced by estradiol would have been detected by the dot immunoblot assay, these data suggest that antiestrogens may have effects on post-translational processing or secretion of vitellogenin in addition to their effects on vitellogenin transcription.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014819:Vitellogenins / Q000096:biosynthesis* / Q000235:genetics; D014982:Xenopus laevis
D004965:Estrogen Antagonists; D012333:RNA, Messenger; D014819:Vitellogenins; D013629:Tamoxifen; C016601:afimoxifene