Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The steroid complexes of (plasma) corticosteroid-binding globulin can be distinguished from intracellular steroid-receptor complexes by agar electrophoresis at low temperature in neuraminidase-treated tissue extracts. With this method, the presence of progesterone receptor has been demonstrated in heavily plasma-protein-contaminated human uterus "cytosol", but not in human mammary carcinoma extracts. SHBG and "basic" receptors for estradiol and dihydrotestosterone in human uterus cytosol could also be assayed simultaneously.
Mol Cell Endocrinol
PMID:Differentiation between steroid hormone receptors CBG and SHBG in human target organ extracts by a single-step assay. 17 88

Using [3H]R5020 as binding probe, we have looked for the presence of progesterone receptors in testis cytosol from a few vertebrate species ranging from the turtles to the humans. In addition, we have tested in the rat several experimental conditions potentially susceptible to induce progesterone receptors. With the exception of chicken, tfm patients and possibly the frogs, progesterone receptors could not be conclusively demonstrated in any of the other animal species tested nor could they be induced in the rat. Surprisingly, they were not present in Stanley-Grumbeck pseudohermaphrodite rats. In chicken testes, the levels of progesterone receptor were variable (3--45 fmol per mg prot.) in the adults and high (87 fmol per mg prot.) in one-day-old animals. The presence of progesterone receptor, a marker of estradiol action in many estrogen-target tissues, seems to be parallel to the capacity of chicken testes for sex reversal under the influence of estrogens. In human tfm, the presence of these receptors could also indicate that the gonads are estrogen-sensitive or that they were so during embryonic life although the nature of estrogenic action is not known.
Mol Cell Endocrinol 1979 Oct
PMID:Search for progesterone receptors in testes from various animal species. 49 54

The influence of several parameters on the kinetics of activation of the progesterone receptor in the cytosol of rabbit uterus is described. The estimation of the proportion of activated receptor is based on the differential affinity of the activated and non-activated forms of the receptor for phosphocellulose. Under appropriate conditions binding to phosphocellulose can be used as a test of activation and gives results similar to those obtained with DNA--cellulose, or isolated cell nuclei. The kinetics of receptor activation is temperature-dependent and compatible with a first-order reaction at all temperatures tested. The thermodynamic activation energy of this reaction is 67.8 kcal mol-1. The progesterone receptor can be activated to various extents by increased ionic strength or by dilution of the cytosol with buffers of low ionic strength, and in all cases the activation follows apparent first order kinetics. At a concentration of 0.4 M NaCl, 70--80% of the receptor can be converted into the activated form. The activated and non-activated forms of the receptor appear to be in equilibrium. Salt-activated and heat-activated receptor can be transformed to a non-activated form by decreasing either the salt concentration, or the temperature of incubation. The rate of dissociation of the steroid from the activated form of the receptor is indistinguishable from that observed with the non-activated form, but the activated receptor is more thermolabile. Upon centrifugation on sucrose gradients there are no major differences in the sedimentation behaviour of the two forms of the receptor.
Mol Cell Endocrinol 1979 Dec
PMID:Activation of the progesterone receptor of rabbit uterus. 52 Jun 62

Human and rat cDNAs to Clara Cell 10 kDa protein (CC10) have been previously isolated. Comparison of the amino acid sequences showed that CC10 is homologous to rabbit uteroglobin. Here we present further evidence that human CC10 is the human counterpart of rabbit uteroglobin. We have isolated the gene and have mapped its genomic localization to chromosome 11q11-qter. Sequence analysis of the 5'-flanking region reveals that the homology between the human and the rabbit gene starts at the first exon/intron boundary and extends up to -1.4 kb. A second region of 0.74 kb from -1.77 to -2.51 kb in the human 5'-flanking gene region is homologous to rabbit sequences that include four progesterone receptor binding sites which have been implicated in progesterone regulation of rabbit uteroglobin gene expression in endometrium. Sequence alignment of this region on the nucleotide level shows that only two weak progesterone receptor binding sites are partially conserved. In addition, close inspection of the human and rabbit promoters reveals that the estrogen responsive element and two recently identified cis elements of the rabbit promoter located between -177 and -258 bp are also absent in the human uteroglobin promoter. Despite these differences in the 5'-flanking regions of the genes, we report that the human uteroglobin mRNA is expressed in a human cell line of endometrial origin indicating that human uteroglobin is expressed in the uterus like its rabbit homologue. Thus, it appears that human uteroglobin is not only a marker for lung Clara cells but also an endometrial differentiation marker.(ABSTRACT TRUNCATED AT 250 WORDS)
Hum Mol Genet 1992 Sep
PMID:Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines. 128 26

The antiestrogen tamoxifen has been successfully used to control estrogen receptor (ER) and progesterone receptor positive breast cancer. However, the development of antiestrogen resistance is frequently observed in patients following long term treatment. We have studied the development of antiestrogen resistance in vitro and established an antiestrogen resistant variant of MCF-7 cells (clone 5C) after long term culture in estrogen free medium. The growth of clone 5C cells was not altered by either estradiol-17 beta or the antiestrogens 4-hydroxytamoxifen and ICI 164,384. Estrogen-stimulated progesterone receptor and reporter gene expression were markedly reduced in 5C cells compared to wild type MCF-7 cells. Only minor alteration in the levels of ER and no alteration in the affinity of ER for ligand were found in 5C cells. No mutation of ER cDNA in 5C cells was detected by polymerase chain reaction and DNA sequencing. This study demonstrates that change(s) in ER-mediated gene expression rather than the amino acid sequence of the ER itself may be associated with the development of at least one form of antiestrogen resistance.
Mol Cell Endocrinol 1992 Dec
PMID:An estrogen receptor positive MCF-7 clone that is resistant to antiestrogens and estradiol. 130

Gene regulation by steroid hormones leads to induction or repression of particular sets of genes. These effects are mediated by intracellular hormone receptors that, in the unliganded state, are maintained in an inactive form by unknown mechanisms possibly involving association with other cellular proteins. Induction of the mouse mammary tumor virus (MMTV) requires binding of the hormone receptor to a complex hormone-responsive element (HRE) located between 75 and 190 bp upstream from the start of transcription. The interaction of several receptor molecules with the four receptor binding sites in the HRE is highly cooperative on circular DNA molecules and each individual site is needed for optimal induction. In chromatin the HRE is precisely organized in phased nucleosomes. Following hormone treatment and receptor binding, changes in chromatin structure are detected that correlate with binding of transcription factors, including nuclear factor I, to the MMTV promoter. However, though nuclear factor I acts as a basal transcription factor on the MMTV promoter it does not cooperate with the hormone receptors in terms of binding to free DNA, and mutation of the nuclear factor I binding site does not eliminate hormonal stimulation. This residual induction is mediated by octamer motifs, upstream of the TATA box, that bind the ubiquitous transcription factor OTF-1. Mutation of these octamer motifs does not influence basal transcription in vitro, but completely abolishes the stimulatory effect of progesterone receptor.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Transcriptional control by steroid hormones. 131 74

Using high resolution isoelectric focusing we have been able to identify a low affinity/high capacity oestrogen binding protein, which exhibits an apparent pI of 7.0. Using this system it can be separated from the previously described high affinity oestrogen receptor (ER) isoforms which focus at pI 6.1, 6.3, 6.6 and 6.8. The pI 7.0 protein was detected in 30/30 breast tumours analysed and had the binding characteristics of the cytoplasmic Type II ER (Kd = 88 +/- 8 nM). The concentration of this protein was shown to be significantly correlated with the concentration of the pI 6.6 species, which represents the major 4S isoform. It is not related to any other isoform of ER, and is expressed independently of the progesterone receptor. The importance of this observed relationship with respect to ER function remains obscure, but it may provide new insights into the role of the Type II oestrogen binding site in breast cancer.
J Steroid Biochem Mol Biol 1992 Aug
PMID:Type II oestrogen binding site is associated with the major 4S oestrogen receptor isoform in breast tumours. 132 97

The mouse mammary tumor virus (MMTV) promoter, that responds to glucocorticoids and progestins, contains a complex hormone response element (HRE) in the long terminal repeat (LTR) region covered by a phased nucleosome. Hormone treatment leads to alterations in chromatin structure that make the HRE region more accessible to digestion by DNase I and permit binding of transcription factors, including nuclear factor I (NFI), immediately downstream of the HRE. NFI acts as a basal transcription factor on the MMTV promoter in vitro but competes with the hormone receptors in terms of binding to free DNA. In uninduced chromatin, the precise positioning of the DNA double helix on the surface of the histone octamer precludes binding of NFI to its cognate sequence while still allowing recognition of the HRE by the hormone receptors. We postulate that receptor binding to the nucleosomally organized MMTV promoter disrupts the chromatin structure enabling NFI binding and subsequent formation of a stable transcription complex. Whether the receptor remains bound to DNA during induction or is displaced by NFI is not conclusively known, but our evidence supports a "hit and run" mechanism. NFI is not the only factor involved in hormonally induced transcription of the MMTV promoter. Two degenerated octamer motifs located immediately upstream of the TATA box are recognized by the ubiquitous transcription factor OTF-1 (Oct-1, NFIII), and are also important. In vitro, mutations in these motifs do not influence basal transcription, but completely abolish the stimulatory effect of purified progesterone receptor. Progesterone receptor bound to the HRE facilitates binding of OTF-1 to the two octamer motifs. Thus, OTF-1 is a natural mediator of progesterone induction of the MMTV promoter and acts through cooperation with the hormone receptor for binding to DNA.
J Steroid Biochem Mol Biol 1992 Oct
PMID:Interplay of steroid hormone receptors and transcription factors on the mouse mammary tumor virus promoter. 132 70

In an attempt to examine regional synthesis of the progesterone receptor (PR) in the brain, the distribution of mRNA encoding PR was investigated in the female adult rat di- and telencephalon by in situ hybridization using T7 RNA polymerase transcripts of a 320 base pair rat PR cDNA clone. The rat PR cDNA had been partially cloned and sequenced by using the reverse transcription-polymerase chain reaction (RT-PCR) method. The primer set corresponds to a part of the progesterone binding domain of human PR cDNA. Large numbers of strong labeling were observed in the arcuate nucleus, medial preoptic nucleus, and ventrolateral part of the ventromedial nucleus which are relative to sexual behavior. Moderate labeling was found in layers II and IV of the isocortex, in the pyramidal layer of the CA1 and CA3 fields of the hippocampal formation, in the cortical nucleus of the amygdala, in the nucleus of the diagonal band, and in the anterior periventricular nucleus. Weak labeling was found in many other regions. These results were largely in agreement with the distribution of PR previously reported by ligand binding assay and autoradiographic studies. This present in situ hybridization study may provide a useful tool for the analysis of the regional regulation of PR synthesis in the rat brain.
Brain Res Mol Brain Res 1992 Jul
PMID:Distribution of cells containing progesterone receptor mRNA in the female rat di- and telencephalon: an in situ hybridization study. 133 52

The study of transcription activation by a series of RU486-related 11 beta-substituted progestins revealed three types of ligands: agonists, antagonists, and a novel type of compounds that exerted a mixed activity. These ligands conferred to the human progesterone receptor (hPR) only weak activation properties despite high affinity binding and, hence, acted as agonists and, at the same time, as partial antagonists of pure agonists. When the same series of ligands was tested with mutant PRs, transcriptional activation/inactivation profiles were different from those seen with the wild-type PR, since several steroids initially classified as antagonists switched to mixed responses. One compound that acted as an antagonist for the hPR was an agonist for a mutated PR in which 15 amino acids of the hormone-binding domain were replaced by the corresponding divergent residues of the chicken homolog. In analyzing a series of steroids with wild-type and mutant PRs, we observed that a phenyl group (or a phenyl derivative) in the 11 beta position of RU486-related steroids generates antagonism with hPR, but has to be bound in a critical position in the hormone-binding domain to exert its antagonistic activity. Apparently, a deviation from this positioning by mutations in the hormone-binding domain can generate mixed or even agonistic activities.
Mol Endocrinol 1992 Dec
PMID:Switching agonistic, antagonistic, and mixed transcriptional responses to 11 beta-substituted progestins by mutation of the progesterone receptor. 133 43


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