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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified a specific progesterone receptor in 11 of 33 human breast cancer cytosols. Since progesterone itself binds to glucocorticoid receptor, to corticosteroid binding globulin (CBG), and to nonspecific components as well as to its own receptor, we have used a synthetic progestin, R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), whose binding specificity is restricted to progesterone receptor. Bound R5020 sediments at 8 S in sucrose gradients; binding is competed by excess unlabeled R5020 or progesterone. The receptor is distinct from glucocorticoid receptor and CBG as determined by competition studies using dexamethasone and hydrocortisone. The dissociation constant for R5020 obtained by Scatchard analysis of dextran-coated charcoal assays is approximately 2 times 10- minus 9 M.
Steroids 1975 Apr
PMID:Specific progesterone receptors in human breast cancer. 16 96

We have identified receptors for glucocorticoids, progestins, and androgens in a human breast tumor cell line (MCF-7) known to have estrogen receptor. Sucrose density gradients show that MCF-7 cytosol contains approximately 100 fm/mg protein estradiol (E2-3H) receptor, more than 300 fm/mg protein progesterone receptor (measured with R5020-3H), about 40 fm/mg protein 5alpha-dihydrotestosterone (5alpha-DHT-3H) receptor, and 800 fm/mg glucocorticoid receptor (measured with dexamethasone-3H). Dissociation constants obtained by Scatchard analyses were approximately 0.6 x 10(-10)M (E2), 1 x 10(-9)M (R5020), 2.8 x 10(-10)M (5alpha-DHT) and 8 x 10(-9)M (dexamethasone). No cross competition was found for estrogen receptor, but progestins competed for androgen and glucocorticoid binding. The androgen, but not the glucocorticoid, partially competed for R5020 binding to progesterone receptor. This first demonstration of 4 classes of steroid receptors in human breast cancer means that MCF-7 may be an excellent in vitro model for studying the mechanism of tumor response to endocrine therapy as well as the complex relationships between binding and biological actions of these hormones.
Steroids 1975 Dec
PMID:MCF-7; a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. 17 27

Previous studies on cytoplasmic glucocorticoid receptors and enzyme induction led to the classification of steroids as inducers (optimal or sub-optimal), antagonists, or inactive steroids, with respect to their activity as glucocorticoids. The receptor was postulated to exist in allosteric equilibrium between two conformational states, one "active" and the other "inactive". Steroids behaved as inducers (optimal or sub-optimal), antagonists, or inactive steroids depending on their relative affinity for the active and inactive conformational state of the receptor. Another possible model would invoke multiple binding sites on a single receptor with interactions between the binding sites depending upon the particular steroid bound. To test this latter possibility, an experimental technique was developed to measure the rate of dissociation of tritiated dexamethasone ([3H]DM) or tritiated aldosterone ([3H]A) from the glucocorticoid receptor of rat liver or kidney cytosol. The dissociation of the [3H]DM-receptor at 25 C was not due to irreversible denaturation, and minimal recombination of the receptor with [3H]DM occurred. Progesterone and a number of other steroids consistently and significantly increased the dissociation rate of [3H]DM-receptor complexes in both liver and kidney cytosol. An identical effect was seen with hepatic glucocorticoid receptors labelled with [3H]A, like dexamethasone an optimal inducer. All steroids which enhanced glucocorticoid-receptor dissociation were either antagonists or sub-optimal inducers. Thus, it is postulated that glucocorticoid receptors have at least two classes of binding sites, and that occupation of the second site increases the dissociation rate of agonists from glucocorticoid receptors.
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PMID:Glucocorticoid receptors: evidence for a second, non-glucocorticoid binding site. 18 Dec 39

Cytosolic receptor for glucocorticoids can exist in either the free or bound form; assays now in use measure only the free form. In order to assay the total glucocorticoid receptor content of rat liver, free plus bound, we have developed an exchange assay wherein specifically bound [3H]dexamethasone is shown to be a valid measure of receptor in the presence of high concentrations of corticosterone. The exchange between [3H]dexamethasone and corticosterone is able to proceed because, unter the conditions of the assay, corticosterone is almost completely metabolized.
Steroids 1978 Mar
PMID:An exchange assay for the cytoplasmic glucocorticoid receptor in the liver of the rat. 66 77

Glucocorticoids are final effectors of the stress response. These hormones exert negative feedback action at multiple levels of the hypothalamic-pituitary-adrenal axis and regulate a large number of central nervous system and peripheral target genes. The inactive form of the glucocorticoid receptor in the cytoplasm appears to be bound to heat shock proteins of the 90K family (hsp90 alpha and hsp90 beta). This interaction facilitates binding of glucocorticoid to its receptor and, therefore, its activation. The chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds on a negative glucocorticoid response element in the 5' regulatory region of the proopiomelanocortin gene and prevents the repressive effect of glucocorticoids on this gene. The aim of this study was to examine the effect of glucocorticoids on the steady-state mRNAs of their own receptor, the two hsp90s, and COUP-TF. Quantitative Northern blot analysis in primary leukocytes and Epstein-Barr virus-transformed human lymphocytes (EBV-THL) basally and after a 24-hour exposure to 50 nM dexamethasone was performed. Treatment of primary leukocytes or normally growing EBV-THL with dexamethasone had no effect on the mRNA level of glucocorticoid receptor, hsp90 alpha, hsp90 beta, or COUP-TF. Similar treatment of EBV-THL grown in charcoal-stripped media, resulted in minimal changes in the mRNAs of these factors. Our findings suggest that glucocorticoids do not regulate the steady-state mRNA levels of these core components of the mammalian stress response in human primary and Epstein-Barr virus-transformed lymphocytes.
Steroids 1992 Jun
PMID:Lack of dexamethasone modulation of mRNAs involved in the glucocorticoid signal transduction pathway in two cell systems. 127 41

Glucocorticoid receptors and glucocorticoid receptor RNA (GR RNA) were measured in doxorubicin resistant myeloma cell lines to investigate the relationship between multi-drug resistance and glucocorticoid sensitivity. Glucocorticoid binding sites and GR RNA were found to be lowered in all the tested doxorubicin resistant cell lines: R10, R40 and R60 compared to the untreated wild type RPMI 8226 cells (Dalton, et al., 1984). The least resistant cell line, R10, maintained a down regulation of GR RNA after 48 hours of dexamethasone (10(-6) M) treatment of the cells. Interestingly, the R10 cell line has been reported to be very sensitive to dexamethasone treatment. However, the GR RNA levels increased in presence of dexamethasone in the most resistant cell line, R40, R60 by comparison to the wild type. Thus, the reduction of GR RNA by doxorubicin treatment appears to be overcome by dexamethasone in the most resistant cell lines. Steroids may be helpful in reversing resistance and maintaining drug sensitive human tumor populations that will continue to respond to cancer chemotherapeutic agents.
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PMID:Dexamethasone reverses glucocorticoid receptor RNA depression in multi-drug resistant (MDR) myeloma cell lines. 134 65

The steroidal 20-carboxamides [(20R)- and (20S)-21-(N-substituted amino)-11 beta,17,20-trihydroxy-3,21-dioxo-1,4-pregnadiene] recently have been shown to possess anti-inflammatory activity in animal models of inflammation. These N-substituted methyl, ethyl, n-propyl, and benzyl derivatives also exhibited suppressive effects on plasma corticosterone and thymus function. Generally, the (20R)-hydroxy-20-carboxamides were more potent than the corresponding (20S)-epimers. In continuing investigations on the glucocorticoid effects of these compounds, we have studied their ability to induce tyrosine aminotransferase (TAT), inhibit uptake of [3H]thymidine into DNA, and complete with [3H] dexamethasone for binding to the hepatoma tissue culture glucocorticoid receptor. Results indicated that the N-substituted methyl, ethyl, and n-propyl derivatives were full glucocorticoid agonists in the three measurements. Receptor binding affinities of the N-substituted carboxamides correlated well with their ability to induce TAT activity and to inhibit thymocyte proliferation. Structure-activity relationships indicated that the larger the N-substituent, the weaker the agonist activity in this system, and 20R isomers exhibited higher glucocorticoid agonist activity than the corresponding 20S isomers. This investigation is part of our effort to elucidate structure-activity relationships of steroidal carboxamides synthesized on the basis of the antedrug concept.
Steroids 1992 Jul
PMID:Enzyme induction and receptor-binding affinity of steroidal 20-carboxamides in rat hepatoma tissue culture cells. 135 84

It has long been recognized that cannabinoids, including delta 9-tetrahydrocannabinol (THC), the major psychoactive substance of marijuana, bear structural similarities to steroid hormones. The hippocampal region of the brain is particularly rich in glucocorticoid receptors (GCRs), and the region also displays dense autoradiographic binding by synthetic cannabinoids. The present report summarizes studies conducted on cannabinoid interaction with hippocampal GCRs, both in vivo and in vitro. Young rats treated for 8 months with THC displayed anatomic and cellular changes in the hippocampus similar to those seen in older, untreated rats, or in rats treated with high levels of glucocorticoids. Binding of [3H]dexamethasone in cytosol prepared from adrenalectomized rat hippocampus was reduced in the presence of 100-fold molar excess of unlabeled THC. However, further increases of THC concentration, to 20,000-fold excess, could displace no more than 50% of radiolabeled dexamethasone. Scatchard analysis of the binding produced a parallel competition plot for THC, versus the plot for dexamethasone, which may reflect a noncompetitive or allosteric interaction with hippocampal GCR. Cannabidiol, a nonpsychoactive cannabinoid, displayed less competition than THC in all parameters. Treatment of adrenalectomized rats for 14 days with 10 mg/kg THC produced down-regulation of hippocampal GCR binding in a manner also reported following high glucocorticoid administration. Although an initial oral administration of THC to intact rats stimulated release of plasma corticosterone, daily repetition of treatment for 7 and 14 days failed to elicit further corticosterone secretion. Taken together, the results indicate that THC may possess some agonist-like properties of glucocorticoids at the hippocampal GCR site.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1991 May
PMID:Cannabinoids and the hippocampal glucocorticoid receptor: recent findings and possible significance. 165 67

The precise mechanism for glucocorticoid-mediated lymphocytolysis is not understood, although it is presumed to be receptor mediated. We have recently presented evidence that this response is mediated by a specialized form of the glucocorticoid receptor (GR) that resides in the plasma membrane (mGR). Confirmation of the previous receptor identification studies in a population of S-49 cells enriched for mGR is now made using another antibody specific for the rodent GR, BUGR-2. The membrane resident receptor could be labeled competitively with the affinity ligand dexamethasone 21-mesylate, and Scatchard analysis of whole cell binding revealed that receptor number, but not the affinity for hormone, varied between the mGR-enriched and -deficient cell populations. Steroid specificity displacement analyses showed an order of affinities as follows: triamcinolone acetonide greater than progesterone greater than dexamethasone greater than testosterone = estrogen. Studies of mGR by one- and two-dimensional gel electrophoresis, immunoblot, autoradiography, and density gradients revealed a species with an equivalent size to cytosolic receptor as well as multiple higher molecular weight species, confirming earlier studies. To offer a possible explanation for the nucleic acid origins of the mGR, RNA from the mGR-enriched cells was probed with rat GR cDNA; mGR-enriched cells contained higher levels of GR mRNA. Possible molecular etiologies of larger receptor species in membrane are discussed.
Steroids 1991 Aug
PMID:Size and steroid-binding characterization of membrane-associated glucocorticoid receptor in S-49 lymphoma cells. 178 58

The presence of glucocorticoid receptors is required for glucocorticoid-mediated lymphocytolysis to take place. However, the explicit mechanism of involvement of this receptor continues to be debated. We have recently presented evidence that this response is mediated by a specialized form of the glucocorticoid receptor that resides in the plasma membrane (mGR). Using sequential cell separation techniques ("immunopanning," fluorescent cell sorting, and soft agar cloning), a resultant population of membrane receptor-enriched cells have remained stable and provided material for further analysis. The mGR patching and capping phenomenon originally observed with fluoresceinated monoclonal antibody techniques was verified here with electron micrographic analysis using colloidal gold-conjugated antibody. Using 3H-labeled monoclonal antibody, a radioimmunoassay for membrane receptors was developed. Trypsin treatment removed the membrane receptor antigenic site from the surface of cells. Peptide mapping of receptor purified from plasma membranes reveals several trypsin and alpha-chymotrypsin cleavage sites. Larger fragments resulted from cleavage of the membrane receptor of cells enriched for mGR versus those found in cells depleted of the membrane form, although most of the resulting fragments are shared by the two forms. Confirmation of previous studies correlating membrane receptor with the mechanism of glucocorticoid sensitivity is now extended to include elimination of the lymphocytolysis effect in membrane receptor-stripped (trypsinized) S-49 cells.
Steroids 1991 Aug
PMID:Studies on the arrangement of glucocorticoid receptors in the plasma membrane of S-49 lymphoma cells. 178 59


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