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

In this report we describe experiments showing that diethylpyrocarbonate, a histidine selective reagent, inhibits progestin binding to the chick oviduct progesterone receptor. Because this inhibition is reversed by hydroxylamine, we suggest that the chick oviduct progesterone receptor contains one or more histidine residues that regulate progestin binding. We also find that the progestin R5020 protects the progesterone receptor from diethylpyrocarbonate mediated inhibition of progestin binding. From this we infer that the progestin binding site contains a histidine residue(s) important for progesterone binding to its receptor in chick oviduct.
Steroids 1983 Dec
PMID:Diethylpyrocarbonate, a histidine selective reagent, inhibits progestin binding to chick oviduct cytosol. 668 16

The translocation of progesterone receptor from the cytosol into the nucleus was studied under "in vivo" and "in vitro" conditions in the uteri of guinea pig fetuses exposed to progesterone or a synthetic progestin, R5020. Progesterone treatment of estrogen-primed fetuses leads to a rapid (before 1h) transfer of cytosol progesterone receptor into the nucleus which is, however, short-lived (less than 3h). A rapid decrease in the retention of the estrogen receptor in the nucleus also occurs. In the "in vitro" incubations of whole fetal uteri, translocation of progesterone receptor is temperature-dependent and specific for progesterone and R5020; estradiol and cortisol have no effect. Putative progesterone receptors can also be induced in explants of fetal guinea pig uteri in organ culture which translocate from the cytosol into the nucleus under the same "in vitro" conditions as in whole uteri. Fetal uterine progesterone receptor, either stimulated "in vivo" by estrogen-priming or induced in organ culture, translocates from the cytosol into the nucleus and this process seems to be accompanied by a decrease in retention of the estrogen receptor in the nucleus which appears to be the mechanism by which progesterone antagonises estrogen action in fetal guinea pig uterus.
Steroids 1982 Apr
PMID:Characteristics of the nuclear translocation of progesterone receptor in fetal guinea pig uterus "in vivo", "in vitro" and in organ culture. 689 Nov 22

The equilibrium affinity constant for rat prostate androgen receptor and epididymal androgen binding protein (ABP) has been determined for thirty-four potential progestogens. Three A-nor-, four A,19-dinor-, and one A-homo-5 alpha-androstane derivative bind to the androgen receptor (KD less than 0.5 muM). Five of these compounds also bind to ABP with an affinity of the same order of magnitude. "Anordrin" (compound 24) and "Dinordrins" (compounds 10, 14, 15, 16, 17), which are potential female contraceptives, do not bind with high affinity to the androgen receptor or to ABP. The following modifications in A-nor derivatives favour binding to the receptor as compared to ABP: 19-nor substitution (compound 1), C-18 methyl homologation (compound 5), 2 alpha-ethinylation (compound 22). One 2 alpha-allenyl A-nor derivative (compound 25) and one A-homo derivative (compound 34) bind almost exclusively to ABP. The interaction with either binding protein is decreased by oxidation or esterification of the hydroxyl group at C-17, and by addition of a 17 alpha-ethinyl group. The latter modifications are likely to increase the specificity of androstane derivatives for receptors other than androgen binding proteins, such as the progesterone receptor.
Steroids 1981 Apr
PMID:Interaction of A-nor, A, 19-dinor, and A-homo-5 alpha-androstane derivatives with the androgen receptor and the epididymal androgen-binding protein. 689 53

Estrogen receptor (ER) levels, formation of 3'-phosphoadenosine-5'phosphosulfate (PAPS), and sulfate transfer to estradiol-178, have been determined in 62 human primary carcinoma cytosol preparations. Whilst no differences between ER positive and ER negative tumors were found in the synthesis of [35S]PAPS, formation of estradiol-3-[35S]sulfate catalysed by estrogen sulfotransferase was significantly higher in ER positive tumors [84 +/- 10 (mean +/- S.E.M.) versus 32 +/- 9 pmole estradiol-3-sulfate per mg protein per 2 hr for ER positive and ER negative tumors, respectively, p less than 0.02]. By choosing a discriminating value for estrogen sulfurylation of 40 pmole per mg protein per 2 hr, then 16/19 (84%) of the ER negative tumors were below this point. Since previous data had shown that 20/23 (87%) progesterone receptor negative tumors were also below this value (Pewnim, Adams and Ho, CANCER RES. 40, 1360 (1980), an alternative simple method, having a high potential for the evaluation of hormone responsiveness in mammary cancer, is suggested.
Steroids 1982 Jan
PMID:Estrogen sulfurylation as an alternative indicator of hormone dependence in human breast cancer. 695 16

The effect of sodium molybdate (NaMo) on the ability to detect progesterone and estrogen receptors from human breast cancers was studied. When NaMo was added at 20 mM to cytosols from human breast cancers, progesterone receptor showed major increases by sucrose density gradient centrifugation with tritiated R5020 as ligand. Increases in both 8S and 4S receptors, or in 8S alone, also occurred (reported figuratively). When NaMo addition was analyzed by dextran-coated charcoal method, binding also increased, converting some apparently negative cytosols to positive and increasing the amount of receptor in other positive samples. Additional estrogen receptor could also be measured in some cytosols, and a quantitative temperature-dependent coversion of 8S to 4S binding molecules could be achieved. NaMo prevented loss of binding in 30-degree-incubated cytosols in the absence of added estradiol. NaMo increased amount of progesterone receptor, and to a lesser extent estrogen receptor, but how and why are not known.
Steroids 1980 Mar
PMID:Sodium molybdate increases the amount of progesterone and estrogen receptor detected in certain human breast cancer cytosols. 718 11

The relative binding affinities (RBA) of 51 steroids were determined for the uterine progesterone receptor of the proestrous hamster. The receptor demonstrated a high specificity for progesterone; most structural modifications to the progesterone molecule resulted in a substantial reduction in binding affinity. Only six steroids had relative binding affinities similar to progesterone (RBA=100): 17 alpha-ethinyl-17 beta-methoxy-4-androsten-3-one (RBA=85); 6 alpha-fluoro-4-pregnene-3,20-dione (RBA=94); 17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione (RBA=96); 19-nor-4-pregnene-3,20-dione (RBA=110); 21-fluoro-4-pregnene-3,20-dione (RBA=119); and 17 alpha-ethinyl-17 beta-methoxy-4-estren-3-one (RBA=123).
Steroids 1980 Jun
PMID:Steroid binding specificity of the hamster uterine progesterone receptor. 740 5

Steroids enter target cells and bind to specific receptor proteins. These complexes translocate to the nuclei, bind to the chromatin, and alter gene expression. Recently, inactive progesterone receptors of the chick oviduct have been identified in this laboratory during the late winter which are not capable of translocating and binding to nuclear acceptor sites either in vivo or in a cell free assay. During this period the oviduct remains unresponsive to the steroid. The nuclear binding activity does return at the end of the season with a corresponding return of oviduct responsiveness to the steroid. Analysis of the active and inactive receptors of progesterone reveals no difference in sedimentation rates in high salt or in the affinity of the steroid for the receptor. The tissue levels of the inactive receptor, however, are about-one-half those of the active receptor. Quantitative analysis of the molecular species of the progesterone receptor separated by isoelectric focusing reveals two species for the active receptor preparations (an A species focusing at a pH of 7 and a B species focusing at a pH of 6). The A species was absent in the active receptor preparations which explains the lower amounts of total receptor in this group. Further studies have shown inactive progesterone receptors in the undeveloped oviducts and in the oviducts of estrogen withdrawn chicks. In these instances, the B species of the receptor is missing. The results suggest: (1)a novel regulation of steroid action may exist which acts by modulating the levels of one of the two receptor species (or possible subunits of a dimer); (2)the presence of a steroid receptor does not necessarily reflect that the receptor is functional; and (3)the biological activity of a steroid may be assessed via cell free nuclear binding assays or via analysis of the molecular species.
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PMID:Identification of biologically active and inactive steroid receptors. 746 Feb 67

Circulating concentrations of gonadal steroid hormones and reproductive behavior in female vertebrates vary as a function of ovarian state. Steroids secreted by the ovary, specifically estrogen and progesterone, influence the expression of behaviors associated with reproduction by intracellular sex steroid receptors located in specific regions of the brain. Using in situ hybridization, we analyzed estrogen receptor and progesterone receptor messenger RNA expression in several brain regions of ovariectomized, vitellogenic, and postovulatory individuals from two species of whiptail lizards (Cnemidophorus uniparens and C. inornatus). Although these species are genetically very similar, they differ in two aspects of their reproductive biology: (i) the unisexual C. uniparens alternate between expressing female-typical and male-like pseudosexual behaviors while female C. inornatus normally express only female receptive behavior, and (ii) circulating estradiol concentrations in reproductively active female C. uniparens are approximately five-fold lower than in reproductively active female C. inornatus. We found that the regulation of sex steroid receptor gene expression was region specific, with receptor-mRNA expression being increased, unchanged, or decreased during vitellogenesis depending on the area. Furthermore, several species differences in the amount of sex steroid receptor-mRNA were found that may be relevant to the species differences in circulating estrogen concentrations and sexual behavior.
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PMID:Species differences in estrogen receptor and progesterone receptor-mRNA expression in the brain of sexual and unisexual whiptail lizards. 749 97

The receptor binding of a library of 187 steroids to five steroid hormone receptors (estrogen, progestin, androgen, mineralocorticoid, and glucocorticoid) has been analyzed by correspondence factor analysis (CFA) in order to illustrate how the method could be used to derive structure-activity-relationships from much larger libraries. CFA is a cartographic multivariate technique that provides objective distribution maps of the data after reduction and filtering of redundant information and noise. The key to the analysis of very complex data tables is the formation of barycenters (steroids with one or more common structural fragments) that can be introduced into CFA analyses used as mathematical models. This is possible in CFA because the method uses X2-metrics and is based on the distributional equivalence of the rows and columns of the transformed data matrix. We have thus demonstrated, in purely objective statistical terms, the general conclusions on the specificity of various functional and other groups derived from prior analyses by expert intuition and reasoning. A finer analysis was made of a series of A-ring phenols showing the high degree of glucocorticoid receptor and progesterone receptor binding that can be generated by certain C-11-substitutions despite the presence of the phenolic A-ring characteristic of estrogen receptor-specific binding.
Steroids 1995 Jun
PMID:Correspondence factor analysis of steroid libraries. 767 79

A partial synthesis of the title compound, 4'-(dimethylamino)-17 beta-hydroxy-17 alpha-(1-propynyl)benzo[12,12a]-11 alpha,18-cyclo-12a,12b- dihomo-13 alpha-estr-4-en-3-one 1, is reported. The key step in this synthesis represents an intramolecular alkenylaryl radical cyclization. Treatment of 18-[bromo-5-(dimethylamino)phenyl]gona-5,9(11)-diene-3,17-dione-3, 17- bis[cyclic 1,2-ethanediyl acetal] 5 with tributyl tin hydride and a radical initiator introduces the desired 11 beta,18-bridge. The reduced progesterone receptor affinity of this RU 38 486 analog contributes valuable information to the empirical characterization of the steroid binding site of the receptor protein and explains the observed lack of in vivo antigestational activity.
Steroids 1994 Mar
PMID:Synthesis and biological testing of 4'-(dimethylamino)-17 beta-hydroxy-17 alpha-(1-propynyl)benzo[12,12a]-11 alpha,18-cyclo-12a,12b-dihomo-13 alpha-estr-4-en-3-one: an interesting RU 38 486 analog. 804 50


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