Association of glucocorticoid receptors with prostate nuclear sites for androgen receptors and with androgen response elements.
Ventral prostate glands of intact normal rats contained low levels (2500 molecules/cell) of high-affinity (dissociation constant (Kd) 0.57 nmol/l) glucocorticoid receptors (GR). Levels of GR increased 2.8-fold 1 day after castration, and 4.3-fold 3 days after castration. Nuclear GR increased from a normal value of 1150 molecules/nucleus to 5200 molecules/nucleus 3 days after castration. The greater increase in intranuclear GR was in that associated with oligomeric chromatin. Although nuclear GR never approached the normal population of nuclear androgen receptors (AR; approximately 16000 molecules/nucleus), the selective rise in chromatin-associated receptors ensured that almost 60% of chromatin sites remained occupied. GR associated with prostate nuclear structures in a similar manner to AR, and exogenous GR bound saturably and with high affinity (Kd 100 pmol/l) to a similar number of sites as did AR. Both steroid receptors apparently competed for the same sites. In DNA-cellulose competition analyses, synthetic oligonucleotides containing glucocorticoid response elements or putative androgen response elements competed similarly against immobilized non-specific DNA for both AR and GR. In view of these data and information from other sources, it is probable that the role of GR in the prostate should be assessed with a view to understanding its action under conditions of androgen deprivation.
Davies
P
P
Tenovus Institute for Cancer Research, University of Wales College of Medicine, Heath Park, Cardiff.
Rushmere
N K
NK
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000378:metabolism; D009919:Orchiectomy; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D015854:Up-Regulation
D002843:Chromatin; D009838:Oligodeoxyribonucleotides; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; C028697:dexamethasone receptor; D013196:Dihydrotestosterone; D003907:Dexamethasone