Nuclear translocation of estradiol receptors by the in vivo administration of norethisterone: an alternate mechanism for gonadotropin inhibition.
In order to investigate the anti-gonadotropic effect of norethisterone (NET) in long-term ovariectomized rats, we studied the interaction of this synthetic progestin with intracellular steroid receptors in the anterior pituitary by a nuclear exchange assay. The results demonstrated that the administration of NET to long-term ovariectomized rats resulted in nuclear translocation of estradiol cytosol receptors in the pituitary and uterus with a rate of accumulation and nuclear retention being similar in both tissues. Accumulation of nuclear estradiol receptors in the pituitary was in agreement with the rate of LH inhibition in NET-treated rats. The results presented in this communication may explain the anti-gonadotropic activity of NET in long-term ovariectomized rats in addition to its well known progestational activity.
D000818:Animals; D002369:Castration; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006065:Gonadotropins, Pituitary / Q000037:antagonists & inhibitors*; D007986:Luteinizing Hormone / Q000097:blood; D009640:Norethindrone / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000648:ultrastructure*; D051381:Rats; D011919:Rats, Inbred Strains; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D014599:Uterus / Q000648:ultrastructure
D006065:Gonadotropins, Pituitary; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D004958:Estradiol; D007986:Luteinizing Hormone; D009640:Norethindrone