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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of MCF-7 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) results in an inhibition of cell proliferation and a reduction in the number of estrogen receptors (ER), shown by binding studies and immunoassay. The decrease in ER concentration induced by phorbol ester derivatives parallels their growth inhibitory effect. Moreover, the estrogen receptor of TPA-resistant RPh4 cells (which are insensitive to the antiproliferative and morphological effects of TPA) is not affected by TPA treatment. The reduction in ER concentration appear to be a specific phenomenon since it contrasted with the 2-fold increase in total cell protein content which included an increase in progesterone receptor (PgR). We also found that addition of TPA does not affect estrogen induction of PgR.
Mol Cell Endocrinol 1988 Mar
PMID:Modulation of estrogen receptors by phorbol diesters in human breast MCF-7 cell line. 337 43

We have examined the effects of estrogen and progestin agonist and antagonist ligands on regulation of progesterone receptor (PR) protein and mRNA levels in a variety of human breast cancer cell lines. By Northern blot analysis, using human PR cDNA probes, PR mRNA in T47D and MCF-7 cells appears as five species of approximately 11.4, 5.8, 5.3, 3.5, and 2.8 kilobases. PR mRNA species are not detected in the PR protein-negative breast cancer cell lines MDA-MB-231 and LY2. T47D cells contain high levels of PR mRNA and protein (detected by hormone binding assay or Western blot analysis), and the PR protein and mRNA content of T47D cells are reduced to about 10% of the control level within 48 h of treatment with 10 nM promegestone; 17, 21-dimethyl-19-nor-pregna-4,9-diene-3, 20-dione (R5020) or 16 alpha-ethyl-21-hydroxy-19-nor-pregn-4-ene-3,20-dione (ORG2058), both potent progestins. In contrast, treatment of T47D cells with the antiprogestin 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]-17 alpha-(1-propynyl)-estra- 4, 9-dien-3-one) (RU38486) reduces PR protein and mRNA levels only transiently. PR protein and mRNA are virtually undetectable in control MCF-7 cells grown in the absence of estrogens. When estradiol is administered to MCF-7 cells, the PR mRNA and protein levels increase gradually and proportionately (10- or 40-fold, respectively, in 3 days).(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1988 Mar
PMID:Ligand-modulated regulation of progesterone receptor messenger ribonucleic acid and protein in human breast cancer cell lines. 339 53

It has recently been reported that phenol red, a pH indicator present in most tissue culture media, is a weak estrogen that can stimulate some estrogen-sensitive cells. However, the relative impact of phenol red on various cell lines is controversial. We examined the effect of phenol red on several estrogen-responsive cell systems that we use to study estrogen action. These included estrogenic stimulation of progesterone receptor and growth in human breast cancer-derived MCF-7 cells, stimulation of growth in human breast cancer-derived T47D cells, stimulation of prolactin synthesis in primary cultures of immature rat pituitary cells, and stimulation of progesterone receptor in primary cultures of immature rat uterine cells. Estrogenic responses in MCF-7 cells were the most sensitive to the presence of phenol red, while the other three cell cultures showed lesser effects of the indicator. In addition to intrinsic differences in cell responses, there were several other factors involved. These included differences in the estrogenic activity of phenol red-containing media and phenol red itself from different commercial suppliers, and differences in the concentration of free phenol red in final media due to binding of the indicator by serum. Higher concentrations of serum reduced the impact of phenol red on estrogenic responses in primary pituitary cells. Phenol red added to rat uterine cytosol competed with estradiol for binding to the estrogen receptor (relative binding affinity (RBA) approx. 0.001), and the acidic and basic forms of the indicator showed similar activity. Some commercial phenol red samples inhibited cell growth at levels of 100 mg/l; these effects were toxic rather than antiestrogenic, because growth inhibition could not be competitively reversed by an excess of estradiol. The amount of the indicator bound to serum in the final media, the source of the phenol red and the sensitivity of different cell types to the indicator ultimately determine its influence to the response of cells in tissue culture.
Mol Cell Endocrinol 1988 Jun
PMID:Estrogenic activity of phenol red. 340 60

Previous purifications of the progesterone receptor have yielded inadequate amounts of pure protein along with significant amounts of a nonreceptor contaminant. We have taken advantage of the high yield provided by an affinity chromatography method for partial purification and after the incorporation of additional steps, we obtained purified progesterone receptor devoid of detectable contaminants and suitable for chemical analysis. A polyclonal antibody was obtained using the pure receptor as the antigen. The antibody was specific for progesterone-binding receptor. Tissue distribution of cross-reacting material, analyzed by immunoblotting, confirmed the presence of the receptor protein only in the two tissues where progesterone binding has been described in the chick: the oviduct and the bursa of Fabricius. It was absent in receptor-negative tissues such as liver and lung. The receptor was cleaved with cyanogen bromide and trypsin to obtain fragments that were partially sequenced.
Mol Endocrinol 1987 Mar
PMID:Chemical and antigenic properties of pure 108,000 molecular weight chick progesterone receptor. 345 92

The progesterone receptor from hen oviduct is isolated as a complex of two subunits, A and B. The A protein binds one molecule of progesterone and also binds to DNA with high affinity. The native A protein can be labeled with iodine with no loss of DNA-binding activity. Limited Staphylococcus aureus V8 protease digestion of the labeled preparation results in a number of DNA-binding and non-DNA-binding fragments of the receptor. The progesterone-binding domain contains iodine label. However, two low-molecular-weight DNA-binding fragments do not contain iodine label, indicating a lack of susceptible tyrosine residues near the DNA-binding site of the native receptor. The labeled receptor and its fragments will facilitate studies of the isolated DNA-binding and progesterone-binding domains of the hen A protein as well as of the activity of the native receptor in the presence and absence of hormone.
Mol Cell Biochem 1987 Oct
PMID:Iodination of the progesterone receptor from hen oviduct spares the DNA-binding domain. 348 32

In order to develop imaging agents for receptor-positive tumors of the breast and prostate, we have investigated the binding affinity of several fluorine-substituted steroids in the testosterone and nortestosterone series for the androgen receptor and the progesterone receptor. The 6 alpha- and 11 beta-fluoro-, and 16 alpha-fluoroalkyl-substituted steroids were prepared by an olefin bromofluorination reaction followed by dehydrobromination or reductive debromination. The 17 alpha-fluoromethyl derivatives were prepared by fluoride ion attack on the 17-spiroepoxide or 17-spiro sulfate and the 17 alpha-fluoropropynyl derivative, by reaction of a propargyl alcohol precursor with diethylaminosulfur trifluoride. Of the compounds synthesized, 17 alpha-(3-fluoro-I-propynyl)nortestosterone was found to possess the highest binding affinity and selectivity for the progesterone receptor, and 11 beta-fluoronordihydrotestosterone had the greatest affinity for the androgen receptor. Both receptor systems seem to tolerate reasonably well the substitution of fluorine for hydrogen.
Mol Pharmacol 1987 Sep
PMID:Fluorinated androgens and progestins: molecular probes for androgen and progesterone receptors with potential use in positron emission tomography. 349 64

We tested hamster uterine progesterone receptor (Rp) forms for binding to different chromatin preparations. Similar forms of chick oviduct Rp were used for comparison. Hamster Rp elutes from DEAE-Sephacel in the two peaks, peak I at 115 mM KCl and peak II at 205 mM KCl. Chick Rp peaks I and II elute at 125 mM and 300 mM KCl, respectively. Both chick and hamster peak I displayed a higher level of binding to SDS-stripped chromatin (DNA) than to crude chromatin or 4 M guanidine hydrochloride (GuHCl)-extracted (nucleoacidic protein, NAP) chromatin while peak II bound 50% better to the NAP chromatin than to crude chromatin or DNA. 10 mM molybdate was used to stabilize Rp and to increase Rp recovery. Molybdate-stabilized hamster Rp elutes from DEAE at the peak II position and like peak II, binds poorly to DNA. Since molybdate prevents receptor activation, DNA-Rp interactions require activated Rp. Because molybdate did not prevent Rp binding to NAP chromatin, we conclude that both activated and unactivated Rp bind well to that matrix. Activated hamster Rp could be extracted from crude chromatin, NAP chromatin and DNA with 200 mM KCl. Unactivated Rp was extracted from NAP only with 6 M GuHCl or NaSCN, whereas KCl, glycerol or pyridoxal 5'-phosphate were not able to remove unactivated Rp from NAP. Various Rp forms did not compete with [3H]ORG 2058-Rp for binding to NAP but BSA did compete. Thus a large portion of Rp binding to NAP may represent nonspecific binding rather than binding to a finite number of Rp acceptor sites. These results suggest that the binding of activated Rp to crude chromatin may represent the actual acceptor sites in target cell nuclei. Since the high level of Rp binding sites in NAP chromatin may be an extraction artifact, the involvement of proposed masking proteins in regulating the availability of acceptor sites should be reconsidered. As an alternative to acceptor site regulation, changes in the Rp molecule itself may be important. Rp isolated from hamster uteri on days 1-4 of the estrous cycle was incubated with crude chromatin, NAP chromatin and DNA. The apparent level of Rp binding to chromatin and NAP chromatin increased 2.5-fold from day 1 to day 4, but Rp binding to DNA remained constant. This suggests that ovarian cycle-dependent changes occur in the unactivated Rp which affect its interactions with chromatin, and these changes disappear when receptor is activated.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Endocrinol 1987 Jul
PMID:Characterization of chromatin binding sites for different forms of uterine progesterone receptor. 362 20

Female rabbits on an atherogenic diet were treated with cottonseed oil (control), tamoxifen, testosterone, or progesterone. After 10 weeks the rabbits were killed, the aortas quickly removed, graded for atherosclerosis, and incubated with [14C]proline to determine collagen and elastin synthesis. Rabbits treated with testosterone and progesterone had the greatest degree of atherosclerosis, the highest DPM in hydroxyproline of collagen and elastin, and the greatest accumulation of collagen and elastin in the aorta. Tamoxifen-treated rabbits had less incorporation of radioactivity. In separate experiments aortas of similarly treated rabbits were analyzed for estradiol and progesterone receptor density. These receptors were found to be present, and progesterone and testosterone administration caused a translocation of progesterone receptors from cytosol to nucleus. Results are consistent with the hypothesis that sex hormones can affect the development of atherosclerosis through a direct effect of the hormones on arterial wall to alter collagen and elastin synthesis, the effect being mediated through hormone receptors in the wall.
Exp Mol Pathol 1985 Dec
PMID:A possible mechanism in arterial wall for mediation of sex difference in atherosclerosis. 406 8

Analysis of the purified chick oviduct progesterone receptor using biochemical and immunological approaches indicates that while the 'activated' receptor ('4S') is a mixture of two progestin-binding polypeptides, 'A' (Mr approximately 79 kDa) and 'B' (Mr approximately 110 kDa), the non-activated receptor ('8S') is a population of complexes containing a hormone-binding polypeptide (A or B, but probably not both) bound to a non-hormone-binding protein (Mr approximately 90 kDa). Two molecules of the 90 kDa protein appear to be present in each '8S' receptor molecule. The 90 kDa protein is also associated with the non-activated forms of receptors of other steroid hormones in the chick. Molybdate stabilizes the non-activated receptors, probably by forming weak coordination bonds with radicals provided by the subunits of the '8S' structure. Activation implies separation of the subunits, without a change in their primary structure, and does not require intervention of any protein other than those present in the '8S' receptor form. The presence of ligand at the binding site accelerates the activation process but, in vitro, is not necessary for it to occur. Unlike the non-activated form, activated receptors bind to the cell nuclei. However, histological studies with anti-progesterone receptor antibodies indicate that in the non-hormone-exposed tissue the (non-activated) receptors could be localized in the nuclei.
Mol Cell Endocrinol 1984 Aug
PMID:Chick oviduct progesterone receptor: structure, immunology, function. 620 15

The role of intraovarian progesterone in the control of follicular growth and development remains unclear. The presence of a rat ovary granulosa cell progesterone receptor suggests that progesterone has a direct effect on the follicles. We have previously reported that progestins inhibit FSH-stimulated estrogen production by cultured granulosa cells by inhibiting the FSH induction of the aromatase enzyme. We now report that progestins can inhibit another FSH action on rat granulosa cells; the induction of LH/hCG receptors. The concomitant administration of 10(-5) M R5020, a potent synthetic progestin, with 10 ng/ml FSH during a 2-day culture period inhibits the FSH induction of LH/hCG receptors by 75 +/- 6% (mean +/- S.E.) The progestin inhibition of the induction of LH/hCG receptors is not mediated by its inhibitory action on the induction of aromatase. Scatchard analysis indicates that progestin decreases the number of LH/hCG receptors per cell but has no effect on receptor affinity. Both R5020 and progesterone have a dose-dependent inhibitory effect on the FSH induction of LH/hCG receptors, causing a 30 and 85% decrease in receptor number at concentrations of 10(-6) and 10(-5) M, respectively. The concomitant administration of R5020 with FSH also leads to a significant decrease in the ability of LH to stimulate cAMP production, indicating that progestin is inhibiting the induction of 'functional' LH/hCG receptors. R5020 (10(-5) M) also inhibits by 90% the induction of LH/hCG receptors by cholera toxin and dibutyryl cAmP, indicating that the progestin effect is at a post-cAMP site. Since the induction of LH/hCG receptors by FSH is a necessary event in follicular maturation, these results offer another mechanism by which progestins, at high concentrations, can inhibit follicular growth and development.
Mol Cell Endocrinol 1982 Jan
PMID:Progestins inhibit FSH-induced functional LH receptors in cultured rat granulosa cells. 627 55


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