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

Treatment of immature female rats with estradiol increases uterine levels of c-jun and jun-B mRNAs approx. 10-fold. This effect is specific for estrogenic steroids. The induction of jun transcripts is blocked by actinomycin D but not puromycin, suggesting that the hormonal effect is due at least in part to transcriptional activation. The hormone effect is rapid and peak levels of jun mRNAs are seen within 3 h after treatment. Inductions of jun and fos transcripts in the uterus by estradiol exhibit similar dose response curves (maximum responses at 4 micrograms/kg). Estradiol also elevates uterine levels of jun-D, and this induction is insensitive to puromycin. In vivo treatment with the phorbol ester TPA rapidly elevates uterine levels of fos, jun, and myc transcripts, indicating that expression of these protooncogenes is under non-estrogenic as well as estrogenic regulation in this target tissue. These results suggest that multiple members of the jun and fos protooncogene families may play a role in amplifying the uterine response to estrogens.
J Steroid Biochem Mol Biol 1992 Feb
PMID:Estrogen regulates expression of the jun family of protooncogenes in the uterus. 154 78

Estradiol 17 beta-hydroxysteroid dehydrogenase (E2DH) is the enzyme responsible for the interconversion of estrone (E1), and the more biologically potent steroid, estradiol (E2), and has a crucial role in regulating breast tissue concentrations of E2. It has previously been shown that breast tumor cytosol is able to preferentially stimulate the reductive conversion of E1 to E2 in cultured MCF-7 breast cancer cells. In this study the stimulatory factor(s) from breast tumor cytosol have been partially purified by gel filtration and affinity chromatography. Human serum albumin (HSA) has been identified as a component of this bioactive fraction. Subsequent testing of commercially purified HSA preparations has revealed the ability of some preparations to be highly stimulatory. The albumin present in breast tumor cytosol may therefore be a contributing factor to the observed stimulation of reductive E2DH activity in cultured MCF-7 cells. Such a mechanism may account in part for the higher concentrations of E2 which are observed in breast tumors in vivo.
Mol Cell Endocrinol 1992 Jan
PMID:Identification of albumin in breast tumor cytosol as a factor involved in the stimulation of estradiol 17 beta-hydroxysteroid dehydrogenase (reductive) activity. 155 73

Influences of steroid hormone additions or of their binding by specific antisera on nuclear maturation and subsequent fertilization and cleavage of bovine oocytes were studied in vitro. It was found that progesterone in doses of 50 ng/ml, 250 ng/ml, 1 microgram/ml or 5 micrograms/ml stimulates reinitiation and in doses of 1 or 5 micrograms/ml stimulates further development of meiosis. Antiserum to progesterone had opposite effects on nuclear maturation, but has no influence on the ability of matured oocytes to subsequent fertilization and cleavage. Testosterone additions (10 ng, 100 ng, 1 microgram or 5 micrograms/ml) did not influence nuclear maturation, but antiserum to this hormone inhibited both meiosis reinitiation and completion, as well as lowered the rate of oocytes fertilized and embryos obtained. Estradiol (5, 50, 100 or 500 ng or 5 micrograms/ml) treatment stimulated reinitiation, but not nuclear maturation. Antiserum to estradiol activated both reinitiation, development and completion of meiosis, but the cells matured by estradiol deficit were as a rule uncapable of fertilization and further cleavage. Estradiol addition (1 microgram/ml) to maturation medium together with FSH (10 micrograms/ml) (but not of FSH alone) lead to a significantly higher rate of fertilization and cleavage of matured cells. Results obtained suggest (1) relative independence of reinitiation, further development of nuclear maturation and cytoplasmic maturation regulation in bovine oocytes as well as (2) the involvement of steroid hormones in these three processes.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Involvement of steroid hormones in bovine oocytes maturation in vitro. 156 62

While steroid response is generally restricted by the availability of steroid receptors, the theoretical limits of the response are not known. We have constructed a series of cell lines that stably express the estrogen receptor (ER) at levels up to 5,000,000 ERs per cell and employed these cells to explore the limits of the estrogen response. Several reporter genes with estrogen response elements upstream of the herpes thymidine kinase promoter showed hyperbolic saturation kinetics with increasing ER. Maximum response was 10 times that seen in cell lines with receptor titers comparable to physiological levels. Half-maximal responses required 500,000 receptors per cell, and cells with 5,000,000 ERs showed greater than 90% maximum induction. Estradiol dose-response studies indicated that the receptors are limiting below 500,000 ERs per cell, but at higher ER titers there are spare receptors. In contrast to most reporters, the widely used reporter pA2-CAT, which has 200 base pairs of Xenopus vitellogenin DNA between the response element and the promoter, showed squelching at ER levels beyond 500,000 per cell. Cell lines that expressed ER above this level activated pA2-CAT with a distorted hormone dependence, where saturating ligand concentrations were inhibitory. All reporters displayed squelching when the ER was provided by transient transfection at a level that we judge is 20,000,000 per cell by extrapolation from the behavior of stable cell lines. These findings suggest that saturation of the cellular capacity to mediate an estrogen response and ER-dependent squelching occur at receptor titers well above those encountered in nature. If current models of steroid hormone action are correct, the findings also imply that estrogen response elements are occupied to very small extents under normal conditions.
Mol Endocrinol 1992 Feb
PMID:The limits of the cellular capacity to mediate an estrogen response. 156 62

Estradiol 17 beta-hydroxysteroid dehydrogenase acts to convert estrone to the biologically active estrogen, estradiol, in breast tumors and MCF-7 breast cancer cells in vitro. In this study we have examined the ability of albumin to influence the effect of growth factors (insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha)) and cytokines (interleukin (IL)-1, IL-6) on estradiol 17 beta-hydroxysteroid dehydrogenase activity in MCF-7 cells. IGF-I (80 ng/ml) or albumin (30 micrograms/ml) stimulated estradiol 17 beta-hydroxysteroid dehydrogenase activity by 144% and 102% (p less than 0.01). The combination of IGF-I and albumin, however, produced a marked (704%) synergistic stimulation of estradiol 17 beta-hydroxysteroid dehydrogenase activity. EGF or TGF alpha failed to stimulate estradiol 17 beta-hydroxysteroid dehydrogenase activity and no synergism with albumin was detected. IL-1 (10 ng/ml), but not IL-6, also stimulated estradiol 17 beta-hydroxysteroid dehydrogenase activity and acted synergistically with albumin to stimulate enzyme activity. MCF-7 cells were shown to specifically bind 125I-albumin and binding is increased by pretreatment of cells with IGF-I (80 ng/ml) for 48 h. It is concluded that the synergism that results from treating MCF-7 cells with albumin and IGF-I may result from increased albumin uptake and subsequent biological effect.
Mol Cell Endocrinol 1992 Jun
PMID:Synergistic interaction of growth factors and albumin in regulating estradiol synthesis in breast cancer cells. 163 15

Within the framework of experiments related to the association between dietary fiber and breast cancer an in vitro test system was used to study the binding of estrogens to various fibers (e.g. cholestyramin, lignin and cellulose) and fiber sources (e.g. wheat bran, cereals, seeds and legumes). Furthermore, the in vivo apparent digestibility of the different fiber sources was tested using a mobile nylon bag technique in intestine-cannulated pigs. Estradiol-17 beta (E2) bound more strongly to the various fibers than did estrone (E1), estriol or estrone-3-glucuronide. At increasing pH (greater than 7) binding of both E1 and E2 to wheat bran decreased significantly. Cholestyramine and lignin bound almost all estrogens present in the medium. Linseed (91%), oats (83%), barley chaff (88%) and wheat bran (82%) are other excellent binders of E2. Corn, rye and white wheat flour showed lower binding capacity with a relatively low affinity. Cereals with the highest percentage of lignin in the fiber (greater than 3%) were also the fiber sources with the lowest apparent digestibility. Estrogens bound with the highest affinity (relative to bovine serum albumin) to these fiber sources. Together with wheat bran and lignin, oats, linseed and soybean seem to be products with good perspectives for in vivo evaluation of the lowering effect of dietary fiber on estrogen exposure of estrogen-sensitive tissues.
J Steroid Biochem Mol Biol 1991 May
PMID:In vitro binding of estrogens by dietary fiber and the in vivo apparent digestibility tested in pigs. 164 89

Isolated rat hepatocytes possess a saturable glucocorticoid uptake system with high affinity (Kd value = 2.8 +/- 0.7 x 10(-8) M; 318,000 +/- 80,000 binding sites per cell; 317 fmol/mg protein). The initial rates of uptake decrease by about 30-40% if the cells are incubated simultaneously with [3H]corticosterone and either SH-reagents (N-ethylmaleimide and p-chloromercuriphenylsulphonate, 1 mM), metabolic inhibitors (2,4-dinitrophenol, 1 mM; and antimycin, 0.1 mM) or the Na+/K(+)-ATPase-inhibitors, ouabain and quercetine. These Na+/K(+)-ATPase-blockers exert half-maximal inhibition at 3 x 10(-7) and 3 x 10(-6) M, respectively. A slight increase in K+ concentration and a corresponding decrease in Na+ in the medium leads to a significant reduction in the initial uptake rate. The uptake system from the rat hepatocytes shows a clear steroid specificity, being different from the intracellular receptor. Corticosterone and progesterone are the strongest competitors, cortisol, 5 alpha- and 5 beta-dihydrocorticosterone, 11-deoxycorticosterone, cortisone and testosterone have an intermediate effect and only weak competition is exerted by dexamethasone and by the mineralocorticoid, aldosterone. Estradiol and estrone sulphate as well as the synthetic glucocorticoid triamcinolone acetonide are unable to inhibit initial corticosterone uptake.
J Steroid Biochem Mol Biol 1991 Jun
PMID:Uptake of corticosterone into isolated rat liver cells: possible involvement of Na+/K(+)-ATPase. 164 77

Estradiol-17 beta (E2) is converted exclusively to intracellular metabolites, termed lipoidal estrogens [long chain fatty acid 17 beta-esters (E2-L)], by human mammary cancer tissue and cell lines. In order to further evaluate the biological role of lipoidal estrogens, rates of saturation of the estrogen receptor (ER) along with formation of [3H]E2-L have been measured in human mammary cancer cells exposed to 5 nM [3H]E2. Extensive specific binding of E2 to ER in MCF-7 cells (approximately 37%) and ZR-75-1 cells (approximately 62%) occurred before appreciable synthesis of E2-L was evident and the maximum level of E2-L attained was only 3-9% of the E2 specifically bound to ER. In these ER positive cell lines, and in the ER negative cell line MDA-MB-231, an initial rise in the rate of E2-L formation was followed by a decrease at approximately 6 min and re-establishment of a new rate, indicating turnover of the E2-L fraction by esterification-de-esterification reactions. This data does not support the concept that E2-L acts in the transport of E2 to nuclear receptors, but rather than liberation of E2 from E2-L could serve to maintain occupancy of ER necessary for initiation of DNA synthesis. The esterase, as studied in pooled human mammary cancer tissue, was found to hydrolyse E2-17 beta-long chain fatty acid esters at different rates--the enzyme being less active towards E2-17 beta-stearate compared to E2-17 beta-oleate, -linoleate and -linolenate. Esterase activity was significantly higher in MDA-MB-231 cells compared to MCF-7 cells. Treatment of MCF-7 cells with E2 did not alter the specific activity of the esterase towards E2-17 beta-oleate as substrate. Similarly, addition of dibutyryl c-AMP to ZR-75-1 cell cultures was without effect on E2-L, both during the time when E2-L was accumulating, or during a subsequent phase when E2-L was decreasing following transfer to medium lacking E2. Calcitonin, which increases endogenous c-AMP in MCF-7 cells, had no effect on E2-L in this latter phase using this cell line. Thus, no evidence could be provided that the esterase was under E2 control, or control by polypeptide hormones which utilize c-AMP as a second messenger.
J Steroid Biochem Mol Biol 1991 Nov
PMID:Metabolism of lipoidal derivatives of estradiol-17-beta in human mammary cancer tissue and cell lines. 165 70

It is well established that estrogen modulates central dopamine functions; however, the mechanism of this interaction is still poorly understood. We have used peripheral N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) administration to induce irreversible blockade of dopamine receptors in ovariectomized female rats, which were pretreated with estradiol (10 micrograms, twice each day for 2 weeks) or its vehicle, in order to investigate the effect of estradiol on dopamine receptor repopulation kinetics. As previously observed, chronic estradiol treatment increased both striatal D1 and D2 dopamine receptor densities and left affinities unchanged. Anterior pituitary D2 dopamine receptor density remained unchanged. One day after EEDQ administration, a similar decrease (80%) of [3H]SCH 23390 and [3H]spiperone binding to striatum of estradiol- and vehicle-treated animals was observed. Anterior pituitary D2 dopamine receptor specific binding was reduced by about 50% the day after EEDQ. Recovery after EEDQ administration showed that both receptor production rate and degradation rate constants of anterior pituitary D2 and striatal D1 receptors were slowed after chronic estradiol treatment, whereas recovery rates for striatal D2 dopamine receptors were unaffected. EEDQ administration in vehicle-treated rats did not significantly affect plasma prolactin levels, whereas the combination of estradiol pretreatment and EEDQ administration led to increased plasma prolactin levels, compared with estradiol-treated animals that did not receive EEDQ. This suggests that only a fraction of anterior pituitary dopamine receptors are required for a maximal inhibition of prolactin secretion. Estradiol affected both striatal D1 and D2 dopamine receptor densities but only D1 dopamine receptor repopulation kinetics, suggesting that it may act by different mechanisms on each dopamine receptor. Alternatively, estradiol may affect dopamine receptor interaction. Thus, the present study raises the possibility that a biochemical D1/D2 receptor interaction affects dopamine receptor biosynthesis, turnover, and/or gene expression and that estradiol may influence this dopamine receptor interaction in the striatum.
Mol Pharmacol 1991 May
PMID:Dopamine receptor reappearance after irreversible receptor blockade: effect of chronic estradiol treatment of ovariectomized rats. 167 86

Human breast cancer cells are used extensively for the study of steroid hormone action. It is known that in both receptor positive and receptor negative cell lines there is considerable metabolism of the natural estrogens, estradiol (E2) and estrone (E1) with interconversion of the two steroids and formation of sulphate and glucuronide conjugates. The aim of the present work was to see if the commonly used oral contraceptive steroids (OCS) ethynylestradiol (EE2) and norgestimate (Ngmate) were metabolized in human breast cancer cell lines (MCF-7 and ZR-75-1) and a normal breast cell line (Huma 7). MCF-7, ZR-75-1 and Huma 7 cells were maintained in Dulbeccos Modified Eagles Medium (DMEM) containing foetal calf serum (FCS) insulin and hydrocortisone. In addition, ZR-75-1 cells required epidermal growth factor (EGF) and E2 while MCF-7 cells required only EGF. On reaching confluence cells were transferred to DMEM containing charcoal-stripped FCS, insulin and hydrocortisone. 48 h later this medium was renewed, radiolabelled steroid ([3H]E1; [3H]E2; [3H]EE2, [3H]Ngmate; [3H]E1-SO4; 1 nM; 0.2 microCi) was added and incubation was for 24 or 48 h. Following incubation, the medium was removed and radioactive steroid extracted with ether. Metabolites were analysed by on-line radiometric HPLC. All the cell lines were able to interconvert E1 and E2; the equilibrium favouring the formation of E2 in MCF-7 and ZR-75-1 and E1 in Huma 7 cells. E1 and E2 also underwent phase II metabolism to form their respective estrogen sulphates, this activity being most marked in the Huma 7 cell line. In addition to sulphotransferase activity, the study with E1 sulphate demonstrated sulphatase activity in both normal and cancer cells. There appeared to be no difference in extent of hydrolysis, with both E1 and E2 formed. With EE2 as substrate there was no evidence of phase I metabolism in any of the cell lines but there was conversion to the presumed 3-sulphate conjugate. The percentage formation of this metabolite was very much greater in Human 7 cells (64.1 +/- 9.6% after 24 h) than in MCF-7 and ZR-75-1 cells (7.4 +/- 5.3% and 10.6 +/- 4.1%, respectively after 24 h). In all the cell lines deacetylation of the progestogen Ngmate to norgestrel oxime was complete within 24 h. In addition there was evidence of loss of the oxime moiety to give norgestrel.(ABSTRACT TRUNCATED AT 400 WORDS)
J Steroid Biochem Mol Biol 1991 Oct
PMID:Metabolism of the oral contraceptive steroids ethynylestradiol and norgestimate by normal (Huma 7) and malignant (MCF-7 and ZR-75-1) human breast cells in culture. 191 42


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