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)

Double labelling and Western blot techniques were used to demonstrate phosphorylation of estradiol receptor. Cells in monolayer culture were incubated with [32P]orthophosphate for 18 h followed by covalent whole cell labelling of the estradiol receptor with tritiated tamoxifen aziridine [( 3H]TA). Labelled receptor was precipitated with the monoclonal antibodies H222 or JS 34/32, coupled to protein A-Sepharose, and purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), or transferred to nitrocellulose paper. Receptor protein was detected on the Western blot with the monoclonal antibody H222 and rabbit anti-rat peroxidase conjugate. Phosphorylated receptor was visualized by autoradiography. Tritium and 32P activities were monitored in the gels. Two phosphorylated forms of the receptor (molecular weights 67 and 50 kDa) have been detected in MCF-7 cells. Estradiol treatment of the cells was found to increase phosphorylation of the receptor. In estradiol-treated cells both phosphorylated receptor forms were present mainly in the nuclear extract. Both forms bound [3H]TA as evidence by SDS-PAGE. [3H]TA binding was abolished by excess non-radioactive estradiol. In addition two phosphorylated proteins of approximately 120 and 90 kDa were regularly coprecipitated with receptor in cytosol. These proteins did not bind [3H]TA. The 90 kDa phosphorylated protein was identified as a heat shock protein (hsp-90).
Mol Cell Endocrinol 1990 Nov 12
PMID:Phosphorylation of the estradiol receptor in MCF-7 human breast cancer cells in culture. 228 77

We investigated whether estrogenic recruitment could enhance the antitumor effect of chemotherapy in 165 patients with advanced breast cancer, presumably sensitive to hormonal treatments (ER + and/or PgR + lesions). The therapeutic regimen consisted of: (a) estrogenic suppression by aminoglutethimide 1 g/day + hydrocortisone 40 mg/day; surgical castration in premenopausal patients only; (b) FAC (5FU 500 mg/m2; ADM 50 mg/m2; CPA 500 mg/m2) for 3 weeks; (c) following randomization, exactly 24 h prior to chemotherapy, patients had to take 1 tablet of either placebo (PL) or 50 microgram ethinylestradiol (EE2). Tolerance, responses, time to progression and median survival were identical in both groups. Thus, EE2 before chemotherapy did not contribute to the efficacy of this particular therapeutic regimen, which yielded an overall response rate of 64%. We conclude that the validity of the hormonal recruitment concept has not yet been established in clinical practice, so that this approach remains experimental.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Assessment of estrogenic recruitment before chemotherapy in advanced breast cancer: preliminary results of a double-blind randomized study of the EORTC Breast Cancer Cooperative Group. 228 84

Rhodamine 123 is a lipophilic cationic fluorescent dye that localizes in mitochondria. We found that 17 beta-estradiol changes the ability of GH4C1 cells, clonal rat pituitary tumor cells, to retain rhodamine 123. Cells incubated with 10 micrograms/ml rhodamine 123 for 30 min at 37 C took up about equal amounts of rhodamine 123, as determined by fluorescence microscopy, regardless of whether they had been treated with estradiol. After three 5-min washes at 37 C, cells treated with 1 nM estradiol for 7 days before incubation with rhodamine 123 had lost more fluorescence than untreated cells. We further characterized the effect by flow cytometry. The difference in fluorescence between control and treated cells ranged from 50- to 500-fold. The effect of estradiol was maximal at 10(-10) M and took a week to develop fully. The effect is specific for estradiol, because estradiol and diethylstilbestrol reduced retention of rhodamine 123 fluorescence at 10(-10) M, but the same concentrations of dihydrotestosterone, progesterone, dexamethasone, and cholesterol did not. To test if the effect on rhodamine 123 fluorescence was caused by activation of the multidrug resistance transport system, we examined the effect of estradiol on the retention of daunomycin, a known substrate of the transport system. Estradiol treatment caused a 3-fold decrease in daunomycin fluorescence. We isolated clones resistant to estradiol-induced loss of rhodamine 123 fluorescence by flow cytometry and found that two clones still showed an estradiol-induced decrease in daunomycin fluorescence equivalent to that of the parent line.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Jan
PMID:Estradiol decreases retention of rhodamine 123 fluorescence in GH4C1 pituitary tumor cells. 232 64

Estradiol induces a 70 kDa protein ('EI70') which is synthesized in vivo in the female rat ventromedial hypothalamus (VMH) and transported to the midbrain central gray, suggesting a role for EI70 in the female mating behavior, lordosis. Luteinizing hormone releasing hormone (LHRH), in addition to stimulating gonadotropin release, potentiates pituitary responsiveness to subsequent exposure to LHRH (the 'priming' effect), facilitates lordosis and induces the synthesis of a 70 kDa protein ('LHRH70') in pituitary in vitro. We now report that EI70 precisely co-migrates on two-dimensional (2-D) gels with the pituitary protein induced by LHRH both in vitro and in vivo. Furthermore, both proteins migrate on 2-D gels in the vicinity of a protein recognized after immunoblotting by antibodies to the heat-shock-70 kDa protein family. The induction of a common protein by estrogen or LHRH could represent a common mechanism by which these hormones facilitate secretion, and by which these hormones interact.
Mol Cell Endocrinol 1989 Apr
PMID:Similarity of an estrogen-induced protein and a luteinizing hormone releasing hormone-induced protein. 266 72

We have investigated the influence of steroid hormones on insulin-like growth factor II (IGF-II) expression. Hepatic IGF-II mRNA decreased gradually during postnatal development, reaching adult levels at 3 weeks of age. Treatment of 1-day-old rats for 4 days with 10 micrograms/day of the glucocorticoid dexamethasone (DEX) reduced IGF-II mRNA levels 10-fold in liver and inhibited body weight gain. Estradiol and testosterone did not affect IGF-II expression. A dose-response relationship between IGF-II mRNA levels and the different amounts of DEX injected was seen. IGF-II levels remained low after withdrawal of DEX, indicating an irreversible effect. Albumin expression was increased in newborn rat livers after DEX treatment. Our results suggest that glucocorticoids play an important role in the regulation of IGF-II expression. The mechanism for glucocorticoid-induced reduction of IGF-II mRNA is still unclear; however, our findings indicate that DEX inhibits IGF-II by causing premature differentiation of the liver.
Mol Endocrinol 1989 May
PMID:Developmental and steroid hormonal regulation of insulin-like growth factor II expression. 275 59

The gene for subunit II of cytochrome oxidase is part of the mitochondrial genome. 17 beta-Estradiol, 1 nM, increased the levels of cytochrome oxidase II mRNA in the GH4C1 pituitary tumor cell line; the increases ranged from 3- to 16-fold over controls in different experiments. Insulin, 300 nM, estradiol, 1 nM, and epidermal growth factor, 10 nM, together caused a larger increase in cytochrome oxidase II mRNA accumulation than did estradiol alone. The dose-response relationship for the induction of cytochrome oxidase II mRNA by estradiol was similar to that for PRL mRNA; maximal induction occurred at about 10(-9) M. This concentration is 10-fold greater than that required for maximal stimulation of cell proliferation and of 1C28, another estrogen-inducible mRNA, indicating that the increase in cytochrome oxidase II mRNA is not a result of increasing the growth rate of the cells. The increase in cytochrome oxidase II mRNA was not caused by an increase in the number of copies of the cytochrome oxidase II gene. Estradiol therefore must induce in the mitochondria an increase in transcription or a decrease in degradation of cytochrome oxidase II mRNA.
Mol Endocrinol 1988 Apr
PMID:Estrogen induces accumulation of the mitochondrial ribonucleic acid for subunit II of cytochrome oxidase in pituitary tumor cells. 283 64

The effects of castration and subsequent testosterone and estradiol treatment and of a single injection of ethylene-1,2-dimethanesulphonate (EDS) on the distribution of [2-125I]iodomelatonin ([ 125I]melatonin) binding sites in the male rat brain were investigated. Castration produced a marked testosterone-reversible decrease in [125I]melatonin binding in the male rat brain, particularly in the hypothalamus and hippocampus. In contrast, [125I]melatonin binding in the parietal cortex, medulla-pons and cerebellum was generally unaffected by castration. Estradiol did not reverse the effect of castration on [125I]melatonin binding. A single injection of EDS which causes the destruction of Leydig cells led to a marked decrease in [125I]melatonin binding in the brain of the rats between 3 and 7 days after treatment. This decrease correlated with the decline in serum concentrations of testosterone. Specific [125I]melatonin binding and serum concentrations of testosterone subsequently increased to control levels within 37 days after treatment in accord with the repopulation of Leydig cells. The results clearly show that testosterone regulates the density of melatonin receptors in the hypothalamus and hippocampus of the male rat.
Mol Cell Endocrinol 1988 Dec
PMID:Impact of circulating testosterone on iodomelatonin binding sites in the male rat brain. 285 Sep 53

Using a combination of hormone-binding assays, immunologic techniques, and mRNA hybridizations we have measured the estrogen receptor (ER) content and studied the hormonal regulation of ER mRNA in one estrogen responsive and one estrogen unresponsive breast cancer cell line, MCF-7 and T47Dco, respectively. Estradiol binding could be detected in cytosol from MCF-7 cells but not in T47Dco cells. However, when measured by an enzyme-linked immunosorbent assay, T47Dco cells were found to contain approximately 15 fmol ER/mg cytosolic protein or 10% of the ER content in MCF-7 cells. Immunologically reactive ER in T47Dco cells was indistinguishable in size (approximately equal to 68 KD) from the ER in MCF-7 cells, as shown by Western blotting using a monoclonal antihuman ER antibody. Quantification of ER mRNA in MCF-7 and T47Dco cells indicated that T47Dco cells contained approximately 50% of the ER mRNA levels found in MCF-7 cells. This basal level of ER mRNA in T47Dco cells was not decreased by estradiol treatment, as opposed to in MCF-7 cells where estradiol caused 40-60% decrease in the ER mRNA expression. Also, estradiol did not increase the progesterone receptor (PR) mRNA levels in T47Dco cells whereas in MCF-7 cells an approximately 5-fold increase of the PR mRNA levels occurred after estradiol treatment. However, incubation of the cells with the synthetic progestin R5020 decreased the ER mRNA levels to approximately the same degree in both cell lines. In conclusion, we have shown that estrogen down-regulates ER mRNA and up-regulates PR mRNA in MCF-7 cells. Neither of these estrogenic effects were seen in T47Dco cells. It appears that the steroid-resistance in T47Dco cells does not occur as a consequence of a complete absence of ER mRNA or protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Jan
PMID:Hormonal regulation of estrogen receptor messenger ribonucleic acid in T47Dco and MCF-7 breast cancer cells. 291 47

To evaluate the direct inhibitory action of luteinizing hormone-releasing hormone (LH-RH) on the steroidogenesis of the human ovary, the primary cultured human corpus luteum cells were investigated. The following were the effects of the addition of LH-RH: Estradiol (E2) and progesterone were produced and secreted in the cultured corpus luteum cells. In the cytoplasm of the cultured corpus luteum cells, E2 and P-antibody complexes were observed as fine granules by the immunohistochemical staining method. The progesterone production of these cells was not inhibited in the cells cultured with LH-RH 10(-8) Mol alone. The progesterone production of the cells was stimulated in the cells, cultured with gonadotropins (LH, HCG and HMG). The gonadotropin stimulated progesterone production was inhibited by LH-RH administration in the cells. In the short term incubation of the human corpus luteum cell suspension, the cyclic adenosine monophosphate (c-AMP) accumulation of the cells incubated with LH-RH alone did not change, but the gonadotropin-stimulated c-AMP accumulation of the corpus luteum cells was significantly inhibited by LH-RH. Concerning these results, it is concluded that LH-RH inhibits the gonadotropin stimulated progesterone production directly in vitro. It is suggested that the mechanisms of these inhibitory actions of the LH-RH are related to the gonadotropin receptor-adenyl cyclase systems, c-AMP metabolizing enzyme and/or progesterone metabolizing enzyme.
 ...
PMID:[Study on the direct inhibitory action of luteinizing hormone-releasing hormone on the steroidogenesis of cultured human corpus luteum cells]. 300 Nov 99

[14C]Estradiol, [14C]estrone, [14C]progesterone and [3H]prostaglandins (PGs) E2 and F2 alpha, when incubated with myometrial plasma membranes (MPM) at a concentration of 1 X 10(-6) M for 1 h at 37 degrees C, bind into MPM at pmolar concentrations. Unlabeled steroids inhibited [3H]PGE2 and [3H]PGF2 alpha binding to MPM in a dose-dependent manner. Membrane-bound and free steroids or PGs were found to be essentially unchanged under the present incubation conditions. Ca2+ ions up to 10 mM increased steroid binding into MPM. Molecular interactions between steroids and MPM were assessed by measuring the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), and by estimating the changes in the allosteric properties of MPM-bound (Na+ + K+)ATPase by fluoride (F-). Steroids appear to increase the MPM fluidity, evaluated through changes in the Hill coefficient for MPM-bound (Na+ + K+)ATPase by F- and by the fluorescence polarization method. Binding of sex steroids to MPM increased the membrane fluidity and decreased the binding of the uterus stimulatory PGs by membrane receptors. These studies provide a basis for postulating that a 'non-genomic' mechanism of sex steroids induces reduction of uterine contractions.
Mol Cell Endocrinol 1986 May
PMID:Sex steroid and prostaglandin interactions upon the purified rat myometrial plasma membranes. 301 59


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