==================================BSR32==================================
32.  The effect of protein, phosphatide, and carbohydrate diets on
     glucocorticoid receptors in: muscles, liver, uterus, brain, 
     hypophysis of the rat.
1
UI  - 87053174
AU  - Scheidereit C ; Westphal HM ; Carlson C ; Bosshard H ; Beato M
TI  - Molecular model of the interaction between the glucocorticoid receptor
      and the regulatory elements of inducible genes.
AB  - Binding sites for the glucocorticoid receptor in an ecdysone-inducible
      gene from Drosophila melanogaster and in the chicken vitellogenin gene
      are described. A comparison with other binding sites for the
      glucocorticoid receptor, which have been analyzed by methylation
      protection experiments, shows they can be classified into three groups.
      The first group exhibits two blocks of contact points in two subsequent
      turns of the DNA helix, and includes only functional regulatory elements.
      The second group shows an identical contact with the hexanucleotide
      5'-TGTYCT-3', but only half the contact points in the other turn of the
      helix, whereas the third group of sites exhibits only the contact points
      within the conserved hexanucleotide. An analysis of the hydrogen-bonding
      potential of the DNA base pairs along the major groove of 10 binding
      sites shows a very well-conserved pattern and a twofold rotational
      symmetry, suggesting that the array of hydrogen bonds may be a relevant
      aspect of sequence recognition by hormone receptors. A representation of
      the binding sites and contact points by computer graphics suggests the
      interaction of a receptor dimer, in a head-to-head arrangement, with two
      subsequent turns of the B-DNA helix within the glucocorticoid regulatory
      elements.
MH  - Animal ; Base Sequence ; Binding Sites ; Chickens/GENETICS ; Computer
      Graphics ; Drosophila Melanogaster/GENETICS ; DNA-Binding Proteins/
      *PHYSIOLOGY ; Ecdysone/PHYSIOLOGY ; *Genes, Regulator ; Hydrogen Bonding
      ; Receptors, Glucocorticoid/*PHYSIOLOGY ; RNA, Ribosomal/*GENETICS ;
      Structure-Activity Relationship ; Support, Non-U.S. Gov't ; Vitellogenin/
      GENETICS
SO  - DNA 1986 Oct;5(5):383-91
2
UI  - 87016908
AU  - Saluz HP ; Jiricny J ; Jost JP
TI  - Genomic sequencing reveals a positive correlation between the kinetics of
      strand-specific DNA demethylation of the overlapping
      estradiol/glucocorticoid-receptor binding sites and the rate of avian
      vitellogenin mRNA synthesis.
AB  - Genomic sequencing was used to study the extent of cytosine methylation
      of four CpG sites within the regulatory region of the estradiol-inducible
      avian vitellogenin II gene. Three of these sites, two of which lie within
      the estradiol-receptor binding site and one in a short stretch of
      alternating purines and pyrimidines, were initially fully methylated.
      Analysis of DNA isolated from liver nuclei revealed that hormone
      treatment of immature White Leghorn roosters resulted in a demethylation
      of these sites, which occurred initially in only one DNA strand. This
      demethylation correlated well with the induction of vitellogenin mRNA
      synthesis. The demethylation of the complementary DNA strand lagged
      approximately equal to 24 hr behind. The fourth CpG, located within an
      overlapping glucocorticoid-receptor binding site, was already
      hemimethylated at the onset of the experiment. The demethylation of this
      site also occurred with kinetics similar to the rate of vitellogenin mRNA
      synthesis. All four CpGs remained demethylated even after cessation of
      gene transcription. A comparison of the methylation state of these four
      sites in DNA from different tissues demonstrated a clear dependence of
      the demethylation on estradiol. Our results suggest that this
      hormone-dependent event occurs via an active pathway through excision
      repair and/or enzymatic demethylation.
MH  - Animal ; Base Sequence ; Binding Sites ; Chickens ; Cytosine/*ANALOGS &
      DERIVATIVES/PHYSIOLOGY ; DNA/*GENETICS ; Female ; Gene Expression
      Regulation ; Kinetics ; Liver/PHYSIOLOGY ; Male ; Methylation ; Oviducts/
      PHYSIOLOGY ; Receptors, Estrogen/*METABOLISM ; Receptors, Glucocorticoid/
      *METABOLISM ; RNA, Messenger/BIOSYNTHESIS ; Vitellogenin/*GENETICS
SO  - Proc Natl Acad Sci USA 1986 Oct;83(19):7167-71
3
UI  - 86245738
AU  - Quirk SJ ; Gannell JE ; Funder JW
TI  - Adrenocorticoid-dependent alpha-lactalbumin synthesis in rat mammary
      gland explants: antagonist studies.
AB  - Though adrenal steroids are required for the production of
      alpha-lactalbumin by mammary gland explants, the physiological class of
      steroid activity (mineralocorticoid, glucocorticoid) remains to be
      established. alpha-Lactalbumin production by mammary gland explants from
      mid-pregnant rats has been shown in previous studies to be increased by
      high doses of aldosterone, but not by deoxycorticosterone; in six of 11
      experiments corticosterone, the physiological glucocorticoid in the rat,
      elevated alpha-lactalbumin; in five other studies corticosterone had no
      effect. In the present studies the mineralocorticoid antagonist,
      spirolactone, at very high doses (3-10 mumol/l) blocked the stimulatory
      effect on alpha-lactalbumin levels of both 30 nmol/l corticosterone and 3
      nmol/l RU 26988, a pure synthetic glucocorticoid (Type II) receptor
      agonist. Receptor studies, however, indicated that this antagonism is
      consistent with Type II, glucocorticoid receptor occupancy by
      spirolactone. Since deoxycorticosterone is without agonist effect, and
      only very high doses of spirolactone affect alpha-lactalbumin synthesis,
      we conclude that the effect of adrenal steroids on alpha-lactalbumin
      production is a manifestation of glucocorticoid and not mineralocorticoid
      activity.
MH  - Aldosterone/PHARMACODYNAMICS ; Androstanols/PHARMACODYNAMICS ; Animal ;
      Dexamethasone/PHARMACODYNAMICS ; Female ; Glucocorticoids/
      *PHARMACODYNAMICS ; Lactalbumin/*BIOSYNTHESIS ; Mammae/*METABOLISM ;
      Pregnancy ; Rats ; Rats, Inbred Strains ; Receptors, Glucocorticoid/*DRUG
      EFFECTS ; Spironolactone/*PHARMACODYNAMICS ; Support, Non-U.S. Gov't ;
      Tissue Culture
SO  - Clin Exp Pharmacol Physiol 1986 Mar;13(3):233-9
4
UI  - 86206046
AU  - von der Ahe D ; Renoir JM ; Buchou T ; Baulieu EE ; Beato M
TI  - Receptors for glucocorticosteroid and progesterone recognize distinct
      features of a DNA regulatory element.
AB  - The chicken lysozyme gene can be induced in oviduct cells by four classes
      of steroid hormones, including glucocorticosteroids and progestins. The
      glucocorticosteroid receptor of rat liver and the progesterone receptor
      of rabbit uterus both bind, although with different relative affinities,
      to two sites in the promoter region of the chicken lysozyme gene located,
      respectively, between 50 and 80 and between 160 and 200 base pairs
      upstream of the transcription start point. Now we show that the purified
      progesterone binding unit of the chicken oviduct progesterone receptor
      (Mr 110,000, or so-called B subunit) generates a DNase I protection
      pattern ("footprint:) in the promoter-distal site that is longer than the
      footprint generated by the glucocorticosteroid receptor. Methylation
      protection studies within the promoter-distal binding site identify four
      contact points for the chicken progesterone receptor and three contact
      points for the glucocorticosteroid receptor, of which only one is shared
      by both receptors. Computer graphics models allow one to envisage a
      different interaction of each receptor with the B form of the DNA double
      helix.
MH  - Animal ; Chickens ; Deoxyribonuclease I/PHARMACODYNAMICS ; DNA/
      *METABOLISM ; Muramidase/GENETICS ; Nucleic Acid Conformation ; *Promoter
      Regions (Genetics) ; Rabbits ; Rats ; Receptors, Glucocorticoid/ANALYSIS/
      *METABOLISM ; Receptors, Progesterone/ANALYSIS/*METABOLISM ; Support,
      Non-U.S. Gov't
SO  - Proc Natl Acad Sci USA 1986 May;83(9):2817-21
5
UI  - 86201736
AU  - Quirk SJ ; Gannell JE ; Fullerton MJ ; Funder JW
TI  - Mechanisms of biphasic action of glucocorticoids on alpha-lactalbumin
      production by rat mammary gland explants.
AB  - The highly selective Type II glucocorticoid ligand RU28362 showed a clear
      biphasic effect on alpha-lactalbumin (alpha-LA) production in rat mammary
      gland explants, with a peak at 1 nM and a return to basal levels at
      30-300 nM; dexamethasone showed a similar profile. Corticosterone, which
      has a higher affinity for Type I than Type II receptors, produced a
      variable response. In six out of eleven studies this was biphasic, with a
      maximum at 300 nM; in five no increase above baseline was seen. Classical
      Type I receptor ligands--aldosterone and deoxycorticosterone--showed
      responses parallel to their Type II agonist activity. We interpret these
      data as follows occupancy of Type I receptors does not increase alpha-LA
      production the response to selective Type II receptor ligands is truly
      biphasic and one explanation of this pattern may be the existence of both
      "turn-on: and "turn-off: acceptor sites in the nucleus.
MH  - Aldosterone/PHARMACODYNAMICS ; Androstanols/PHARMACODYNAMICS ; Animal ;
      Corticosterone/PHARMACODYNAMICS ; Desoxycorticosterone/PHARMACODYNAMICS ;
      Dose-Response Relationship, Drug ; Female ; Glucocorticoids/
      *PHARMACODYNAMICS ; Lactalbumin/*BIOSYNTHESIS ; Mammae/DRUG EFFECTS/
      *METABOLISM ; Rats ; Receptors, Glucocorticoid/METABOLISM
SO  - J Steroid Biochem 1986 Jan;24(1):413-6
6
UI  - 86201690
AU  - Scheidereit C ; Krauter P ; von der Ahe D ; Janich S ; Rabenau O ; Cato
      AC ; Suske G ; Westphal HM ; Beato M
TI  - Mechanism of gene regulation by steroid hormones.
AB  - A first understanding of the molecular events on the DNA level,
      underlying transcriptional regulation by steroid hormones, has been
      approached in the last 3 years by means of protein/DNA interaction
      studies, using purified receptors. This work summarizes our knowledge of
      how purified glucocorticoid and progestine receptors interact with their
      cognate regulatory elements associated with polymerase II dependent genes
      like mouse mammary tumour virus, the genes encoding human metallothionein
      IIA, chicken lysozyme, human growth hormone and rabbit uteroglobin. The
      resulting data agree with those of functional test systems, that have
      been gene-transfer experiments using stable transformants or transient
      expression. A consensus sequence for the regulatory element of the
      glucocorticoid receptor could be deduced that, in its three-dimensional
      representation, gives an impression of the steric mode of interaction.
      The regulatory elements of the progestine receptor overlap in two
      analysed cases with those of the glucocorticoid receptor, but are not
      identical. Furthermore, also a polymerase I transcribed gene encoding
      ribosomal RNA in the mouse could be shown to contain a glucocorticoid
      regulatory element that is functional in in vitro transcription
      experiments. Finally, the latest strategies are the cloning of the
      glucocorticoid receptor gene and the analysis of receptor-mediated
      topological effects.
MH  - Animal ; Base Sequence ; Binding Sites ; Cloning, Molecular ; *Gene
      Expression Regulation ; Human ; Mammary Cancer Virus/GENETICS ;
      Metallothionein/GENETICS ; Mice ; Muramidase/GENETICS ; Promoter Regions
      (Genetics) ; Rabbits ; Receptors, Glucocorticoid/GENETICS/*PHYSIOLOGY ;
      Receptors, Progesterone/*PHYSIOLOGY ; Repetitive Sequences, Nucleic Acid
      ; Somatotropin/GENETICS ; Support, Non-U.S. Gov't ; Uteroglobin/GENETICS
SO  - J Steroid Biochem 1986 Jan;24(1):19-24