Antiprogestins mediate differential effects on glucocorticoid receptor remodeling of chromatin structure. 1998

C J Fryer, and S K Nordeen, and T K Archer
Department of Ob/Gyn, Biochemistry and Oncology, The University of Western Ontario, London Regional Cancer Centre, London, Ontario N6A 4L6, Canada.

We examined the mechanism(s) by which the progesterone receptor (PR) is able to inhibit glucocorticoid receptor (GR) activation from the mouse mammary tumor virus (MMTV) promoter in vivo. Using specific hormone antagonists, we demonstrate that the PR complexed with an type II antiprogestin blocks glucocorticoid-induced activation of the MMTV promoter. However, when complexed with a type I antiprogestin the PR is unable to block glucocorticoid-induced activation. PR repression of GR activity results from the inhibition of the ability of the GR to remodel chromatin such that the antiprogestin-occupied/PR prevents the glucocorticoid induced assembly of a preinitiation complex at MMTV promoter. These experiments suggest that the specific chromatin organization of the MMTV promoter provides a mechanism for regulating cross-talk between the GR and PR in vivo.

UI MeSH Term Description Entries
D008324 Mammary Tumor Virus, Mouse The type species of BETARETROVIRUS commonly latent in mice. It causes mammary adenocarcinoma in a genetically susceptible strain of mice when the appropriate hormonal influences operate. Bittner Virus,Mammary Cancer Virus,Mouse mammary tumor virus,Mammary Tumor Viruses, Mouse
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011374 Progesterone The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS. Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D011965 Receptors, Glucocorticoid Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example. Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D002843 Chromatin The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell. Chromatins
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D006727 Hormone Antagonists Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. Antagonists, Hormone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription

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