Dephosphorylation of oestradiol nuclear receptor in vitro. A hypothesis on the mechanism of action of non-steroidal anti-oestrogens.
We show that a mouse uterus nuclear phosphatase exists that is capable of inactivating nuclear oestrogen receptor complexed to oestradiol-17 beta in vitro but is ineffective when the receptor is complexed with the two non-steroidal anti-oestrogens, nafoxidine and tamoxifen. We suggest that the long half-life of the tamoxifen-receptor complex versus the short half-life of the oestradiol-receptor complex in uterine nuclei in vivo is the result of the ineffectiveness of the phosphatase in dephosphorylating the anti-oestrogen-receptor complex.
D000818:Animals; D002417:Cattle; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006207:Half-Life; D066298:In Vitro Techniques; D051379:Mice; D009256:Nafoxidine / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D011759:Pyrrolidines; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D013629:Tamoxifen; D009256:Nafoxidine; D004958:Estradiol; D010744:Phosphoric Monoester Hydrolases