Interaction of steroids with the nuclear envelope.
Three approaches have been taken to determine the molecular mechanism by which steroid hormones traverse the nuclear envelope on their way to the genome. The first approach involved characterization of steroid binding to nuclear envelope preparations. We have characterized androgen binding to nuclear envelopes isolated from the rat ventral prostate, the rat liver, and androgen-responsive and androgen-unresponsive cell lines of the Shionogi mouse mammary carcinoma and glucocorticoid binding to rat liver. Relatively high affinity binding sites for steroids have been identified on nuclear envelopes. Importantly, the number and specificity of the sites correlates with the responsiveness of the tissue to the steroid. In the second approach, we have undertaken to identify the steroid binding site directly. As the characteristics of the rat ventral prostate site resembled those of the nuclear androgen receptor, we have begun purifying that receptor and have found fast protein liquid chromatography to be very effective. By affinity labelling studies, the dexamethasone binding site on the rat liver nuclear envelope has been identified as a peptide of molecular weight of approximately 90,000. The third approach we have used is to identify androgen-dependent peptides in nuclear envelope preparations. In both the rat ventral prostate and an androgen-responsive cell line of the Shionogi mouse mammary carcinoma, we have identified abundant androgen-dependent peptides. The relationship of these peptides to the binding sites identified by the first two approaches and their role in steroid transport is being investigated.
D000818:Animals; D001667:Binding, Competitive; D002458:Cell Fractionation; D003851:Deoxyribonucleases; D003907:Dexamethasone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D005260:Female; D006493:Heparin; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D009685:Nuclear Envelope / Q000378:metabolism* / Q000648:ultrastructure; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000302:isolation & purification / Q000378:metabolism*; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology
D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D013256:Steroids; D013196:Dihydrotestosterone; D003907:Dexamethasone; D006493:Heparin; D003851:Deoxyribonucleases