Steroid receptor-nuclear matrix interactions. The role of DNA.
The interaction of sex steroid hormone receptors with the nuclear matrix (NM) of target and non-target tissue was investigated using a simple in vitro binding assay. Steroid receptors can recognize acceptor sites on the NM of target cells; androgen receptor binds with the highest apparent affinity to rat prostate NM; similarly estrogen receptor binds with the highest apparent affinity to uterine NM. Furthermore, the steroid receptor-NM interaction depends upon the hormonal status of the animal. The binding of androgen receptor to rat prostate NM was drastically reduced upon hormone withdrawal (castration) and fully recovered upon hormonal stimulation. When NM were prepared by an alternate method (DNase I digestion prior to high salt extraction) known to digest "active" chromatin, no preferential receptor binding to target tissue NM was observed. Although the NM fraction contains less than 1% of the total nuclear DNA, the matrix-associated DNA sequences seem to be, at least in part, responsible for specific receptor recognition. DNA extracted from the prostate NM was shown to be a potent competitor for androgen receptor binding as measured by DNA-cellulose competition experiments. Moreover, this DNA recognition also depends upon the hormonal status of the animal. These studies are consistent with the notion that hormonal manipulation induces changes in the NM-associated DNA sequences of steroid hormone target tissue.
D000818:Animals; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000648:ultrastructure*; D004247:DNA / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000648:ultrastructure; D008099:Liver / Q000648:ultrastructure; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000648:ultrastructure; D011817:Rabbits; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D004247:DNA