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

The first-order dissociation rate constant, k-, of estradiol from uterine estrogen receptor, measured kin the presence of micromolar concentrations of diethylstilbestrol, increased linearly over a large concentration range (0-300 microM) of diethylstilbestrol. The experimental K- measured appears to be the sum of a basal dissociation rate constant corresponding to the spontaneous dissociation in the absence of diethylstilbestrol, and a diethylstilbestrol-induced dissociation rate constant, which is proportional to both the diethylstilbestrol concentration and the inverse of the cytosol concentration. Diethylstilbestrol induced the dissociation of estradiol in all species studied (lamb, calf and rat) and of estrone and 2 antiestrogens in lamb uterus. Various steroids and triphenylethylene antiestrogens also efficiently induced the dissociation of estradiol from the estrogen receptor. However, the potency of these inducers, which varied greatly, was not correlated with the binding affinity for the estrogen receptor. Structural characteristics and the hydrophobicity of the inducers, however, did appear to be important parameters. The relative efficiency of inducers varied depending on the ligand that was bound to the receptor. This induced dissociation allows the complete dissociation of estrogen receptor-[3H]-ligand complexes in a short time (less than 24 h) at low temperatures without alteration of the level of [3H] ligand bound non-specifically and can therefore be used to measure the [3H] ligand bound to the receptor by exchange at 0-4 degree C. From the specificity and the high doses of inducers required to make possible the observation of a significant effect, we conclude that the induced dissociation probably does not have a biological role.
Mol Cell Endocrinol 1982 Jun
PMID:The dissociation rate of estrogen receptor-ligand complexes is increased by high concentrations of steroids and antiestrogens. 710 68

The direct inhibitory effect of estrogen on ovarian androgen synthesis was investigated. When primary cultures of rat ovarian theca-interstitial cells were grown in defined medium with LH there was a marked increase in androgen synthesis of which 98% was androsterone (control = 11 +/- 2 ng; LH = 1219 +/- 217 ng/ml/10(6) cells). Diethylstilbestrol (DES), estrone (E1), estradiol (E2), and estriol (E3) inhibited LH-stimulated androsterone synthesis by 81%, 81%, 81%, and 47%, respectively. The ED50's of the estrogens were: DES = 4.2 +/- 2.1 X 10(-9) M; E1 = E2 = 9.5 +/- 2.4 X 10(-8) M; and E3 = 3.8 +/- 2.6 X 10(-7) M. The estrogen effect was very rapid (t1/2 = 10 min) and long-lasting. Metabolic studies revealed that estrogen inhibited androsterone, androstenedione, 5 alpha-androstane-3 alpha, 17 beta-diol, and testosterone accumulation by 80%, dehydroepiandrosterone and 17 alpha-hydroxypregnenolone by 40%, 17 alpha-hydroxyprogesterone by 30%, while pregnenolone and progesterone were unchanged. These results prove, for the first time, that estrogen can directly inhibit LH-stimulated androgen production in ovarian theca-interstitial cells and suggest that mechanism involves, at least in part, a rapid selective inhibition of the 17 alpha-hydroxylase/C17-20 desmolase activities.
Mol Cell Endocrinol 1982 Sep
PMID:Direct inhibitory effect of estrogen on LH-stimulated androgen synthesis by ovarian cells cultured in defined medium. 712 21

The hormonal regulation of uterine and oviductal cytoplasmic estrogen and progesterone receptors was studied in immature beagles that were untreated, treated with estradiol-17 beta, or treated sequentially with estradiol and progesterone. Estradiol treatment increased the concentration of estrogen receptors in both tissues. Progesterone receptors were not detectable in the reproductive tract of untreated animals, but increased dramatically under the influence of estradiol. Estrogen withdrawal following estrogen stimulation concomitant estrogen plus progesterone administration, and estrogen withdrawal plus progesterone administration all caused significant reductions in both estrogen and progesterone receptors in uterine oviductal cytosols when compared to estrogen treatment alone. Estrogen withdrawal resembled estrogen plus progesterone administration in reducing both estrogen and progesterone receptor levels, although estrogen withdrawal plus progesterone administration resulted in a further reduction in both receptor concentrations. The same positive and negative relationships between estrogen and progesterone receptor content were observed in uterine cytosols from cycling and ovariectomized adults. These data suggest that estrogen and progesterone regulate their respective receptors and that tissue sensitivity to both steroids may be controlled by mechanisms involving fluctuations in receptor concentration in the reproductive tract of the beagle.
Mol Cell Endocrinol 1981 Feb
PMID:Hormonal regulation of cytoplasmic estrogen and progesterone receptors in the beagle uterus and oviduct. 721 1

Estrogen and progesterone receptors from chick oviduct were compared with respect to their chromatographic behaviour on DEAE-cellulose and their DNA-binding ability to test the general validity of the subunit model from O'Malley and coworkers. Both hormone-receptor complexes can be separated on DEAE-cellulose into 2 components A and B. The 2 progesterone-receptor components appear to occur in equimolar amounts, whereas in the case of the estrogen receptor the amount of component A is always significantly larger. After trypsin treatment the estrogen component B disappears. The remaining A is a receptor fragment with reduced molecular weight. This and other data indicate that the estrogen component B represents an aggregated form of the estrogen receptor and not a receptor subunit. The trypsinated progesterone-receptor fragments, however, are still separable into 2 components, even though also reduced in molecular weight. Our DNA-binding data of the progesterone-receptor components are almost consistent with earlier data from O'Malley and coworkers, even though we find some DNA-binding ability also for component B. Both estrogen-receptor components exhibit affinity for DNA and significantly more than 50% (up to 80%) of the total estrogen-receptor complex are able to bind to DNA. Furthermore we could show that the estrogen-receptor from chick oviduct can be transformed from a DNA-non-binding to a DNA-binding form, similar to other steroid-hormone receptors. This is not compatible with pre-existing receptor subunits in equimolar amounts, one with and the other without affinity for DNA.
Mol Cell Endocrinol 1980 Jul
PMID:The general validity of the subunit model of the progesterone receptor from chick oviduct appears questionable. Comparison of progesterone and estrogen receptor. 739 2

Estrogen receptors (ER) are detected in 50-85% of all breast tumors, and are clinically important because they tend to identify patients with a higher probability of responding to hormonal or endocrine manipulations. However, approximately 30-40% of all ER+ patients do not respond to hormonal manipulations. The lack of response to hormonal manipulations in ER+ patients could be the result of nonfunctional ER, as determined by its inability to recognize and bind to specific DNA-responsive elements and/or its inability to recruit other transcriptional activation factors. The functional status of ER in 34 human breast tumors was assessed determining the structural integrity of the ER DNA-binding domain using site-directed monoclonal anti-estrogen receptor antibody and sucrose density gradient analysis. Based on the fraction of ER containing an intact DNA-binding domain, the tumors were classified into three groups: group I with > 65% of intact ER, group II with > 30% of intact ER, group III with < 30% of intact ER. Clinical and pathologic data were obtained only for patients who were treated with the anti-estrogen tamoxifen and correlated with ER functional status. In group I, 11 of 13 (84.6%) patients were responsive to hormonal therapy with favorable clinical outcome; two patients had unfavorable clinical outcome. In group II, 13 of 15 patients (86.7%) had favourable clinical outcome, and two patients 13.3% had unfavorable outcome. In group III, three of six patients appeared to be hormone responsive with favorable clinical outcome, and three of the patients in this group had unfavorable response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagn Mol Pathol 1995 Sep
PMID:Estrogen receptor functional status in human breast cancer. 749 42

We were previously investigating the expression of the extracellular matrix glycoprotein tenascin in normal and malignant endometrial tissues of humans and rodents. These studies suggested that the expression of tenascin was induced by proliferating epithelia (normal and particularly malignant) and was downregulated with their differentiation. The aim of this study was to investigate the hormone dependency of tenascin expression in (a) the transplantable EnDA endometrial tumor model with or without estrogen deprivation (ovariectomy) of the animals, (b) DMBA-induced rat mammary tumors with or without a hormonal treatment of the animals [ovariectomy, antiestrogen (tamoxifen) or antiprogestin (ZK 98299) treatment] and (c) in the rat prostate of untreated or androgen deprived animals (orchiectomy, flutamide-, casodex- or cyproterone acetate (CPA)-treatment). 1. Estrogen withdrawal by ovariectomy did not affect tenascin expression in transplantable EnDA endometrial adenocarcinoma, meaning the entire extracellular space of the stromal mesenchyme was decorated by tenascin immunoreactivity. 2. In untreated DMBA-induced rat mammary tumors almost the entire extracellular space of the stroma was stained by tenascin immunoreactivity. Ovariectomy and antiestrogen treatment did not affect tenascin expression. In contrast, antiprogestin treatment induced terminal differentiation of mammary tumor cells and in parallel downregulated tenascin expression. 3. In the normal rat prostate no tenascin was detectable by immunocytochemistry. However, following androgen deprivation we found tenascin expression in the stroma of the prostate. The most prominent expression was observable after CPA-treatment, possibly due to its progestagenic potency. In conclusion, the hormones and antihormones tested show no direct effect on the stromal expression of tenascin. However, proliferative activity and a low degree of differentiation of the epithelium induces tenascin expression, whereas epithelial differentiation apparently shuts down tenascin expression. Preliminary in vitro studies suggest that paracrine acting growth factors trigger the hormonal regulation of tenascin expression.
J Steroid Biochem Mol Biol 1994 Apr
PMID:Stromal expression of tenascin is inversely correlated to epithelial differentiation of hormone dependent tissues. 751 33

Antagonists of steroid hormones are clinically important in the management of breast cancer. However, the duration of response is limited due to the development of hormone-independent tumors in virtually all cases. In an attempt to obtain insight into the mechanisms underlying antiestrogen resistance, the consequences of epigenetic changes in gene expression were studied in vitro. Estrogen-dependent ZR-75-1 human breast cancer cells were treated with 5-azacytidine, an inhibitor of DNA methylation, and cultured in the absence of estradiol or in the presence of antiestrogens. Estrogen-independent cell colonies developed within 3 weeks at high frequency in 5-azacytidine-treated cultures (0.7 x 10(-3), in contrast to control cultures (< or = 10(-8). The derived cells (ZR/AZA) were resistant to 4-hydroxytamoxifen and ICI 164,384, independent of the selection protocol, but had lost the ability to grow anchorage-independent. Whereas expression of estrogen receptor, progesterone receptor, and pS2 were down-regulated, expression of epidermal growth factor (EGF) receptor and HER2/neu were increased in ZR/AZA cells. In contrast to the stable altered expression patterns of estrogen receptor and EGF receptor, transient keratin 7 expression was observed. Transforming growth factor-alpha mRNA was identified in ZR-75-1 cells and ZR/AZA cells and EGF-like peptides were secreted in the culture medium. Proliferation of ZR/AZA cells could be partially inhibited with an EGF receptor-blocking antibody. Presence of both growth factor receptors and possible ligands suggests the development of an autocrine growth mechanism. Our data show that epigenetic alterations of gene expression result in rapid progression of breast cancer cells to hormone independence.
Mol Endocrinol 1994 Nov
PMID:Induction of estrogen independence of ZR-75-1 human breast cancer cells by epigenetic alterations. 753 60

Endometrial fibroblasts derived from uterine endometrium as controls and endometrial cancer cells (Ishikawa and HHUA cells) were used to analyze the manner of induction of c-Ha-ras transcripts in endometrial cancers, some of which are estrogen-dependent in growth. Estrogen increased c-Ha-ras expression and tyrosine kinase (TK) activity in fibroblast and Ishikawa cells, but not in HHUA cells. Progesterone diminished c-Ha-ras expression and tyrosine kinase (TK) activity induced by estradiol in the fibroblasts, but not in Ishikawa cells, which persistently overexpressed c-Ha-ras. In these cells, epidermal growth factor (EGF) increased c-Ha-ras expression as did estradiol. Pretreatment with tyrphostin, an inhibitor of TK, abolished estrogen-inducible overexpression of c-Ha-ras. The combination of both estradiol and EGF at maximum effective concentration exerted no additive or synergistic effect on induction of c-Ha-ras expression. In conclusion, persistent activation of TK might lead to overexpression of c-Ha-ras in some endometrial cancer cells under estrogen predominant milieu, which might be associated with the transformation or growth potential.
J Steroid Biochem Mol Biol 1995 Oct
PMID:Estrogen induces c-Ha-ras expression via activation of tyrosine kinase in uterine endometrial fibroblasts and cancer cells. 757 18

Estrogen receptors of human endometrial cancer Ishikawa cells were found to be present in moderate amounts (160-200 fmol/mg protein), and to specifically bind moxestrol (R2858) with a very high affinity characterized by a Kd around 60 pM, when measured under equilibrium conditions. The binding specificity respected a decreasing order as follows: estradiol (E2: 100%) > 4-hydroxy-tamoxifen (4OHTAM: 52.7%) > estriol (E3: 5.7%) > estrone (E1: 2.1%) > TAM (0.2%). The induction of alkaline phosphatase activity (APase) used as an estrogen-specific response, confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT): norethindrone (NOR), norethynodrel and levonorgestrel, at concentrations ranging from 10(-8) to 10(-6) M. The effect of NOR was partially blocked by the antiestrogen 4OHTAM, which was also partially agonistic in this model, but neither by the antiprogestin mifepristone (RU486) nor by the aromatase inhibitor aminoglutethimide. A simulatory effect was also detected at 10(-7) or 10(-6) M with ethindrone, the testosterone- (T) derived progestin homologous to NOR, and with both androgenic parent-compounds, i.e. T and 19NT themselves. In contrast, progesterone (P) derivatives like medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) remained totally inactive, as well as 19-nor-progesterone (19NP) itself or its progestagenic derivatives: ORG 2058 and nomegestrol acetate (NOM). Structure-activity relationships deduced from these studies suggest that it is not the absence of the 19-methyl group which can account for the estrogenic potential of the so-called "19-norprogestins", but rather their steroid structure derived from T in a broad sense (including the 19NT derivatives), as opposed to the non-estrogenic therapeutic progestins derived from P like MPA or CMA, or from 19NP like NOM.
J Steroid Biochem Mol Biol 1995 Oct
PMID:Lack of estrogenic potential of progesterone- or 19-nor-progesterone-derived progestins as opposed to testosterone or 19-nor-testosterone derivatives on endometrial Ishikawa cells. 757 23

Sturgeon are an ancient family (Acipenseridae) of fishes that lie close to the divergence of fish that eventually evolved into terrestrial animals and those that evolved into modern teleost species. Therefore, white sturgeon vitellogenin sequences fill a gap in the current understanding of the functional domains of this protein family. Vitellogenin cDNA was sequenced and used to investigate gene expression in white sturgeon, Acipenser transmontanus. Estrogen-induced vitellogenin mRNA was detected in the livers of both males and females and was also detected in undifferentiated gonads of estrogen-treated fish. Low levels of vitellogenin mRNA were also detected in the testis of both control and estrogen-treated males. The cDNA encoded a 186-kDa protein that was missing only six to seven of the amino-terminal amino acids. Comparisons to silver lamprey, Xenopus, and chicken vitellogenin sequences indicate that the overall structure of the yolk protein domains were highly conserved. There was considerable homology in three regions of the lipovitellin I domain. These conserved sequences are likely to be involved in vitellogenin receptor binding. The phosvitin domain of white sturgeon vitellogenin contained fewer and shorter serine repeats as predicted from yolk protein phosphate content of fish compared to Xenopus and chicken. However, the vitellogenin of white sturgeon had a lower serine content as compared with silver lamprey, indicating that an increased serine content is not strictly a function of evolutionary age.
J Mol Evol 1995 Jul
PMID:Characterization of vitellogenin from white sturgeon, Acipenser transmontanus. 760 84


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