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Query: UNIPROT:P06889 (Mol)
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We have cloned the chicken estrogen receptor (ER) from a chicken oviduct lambda gt11 library using the human ER cDNA sequence. This chicken ER sequence is virtually identical to the recently published sequence. One noteable difference is an amino acid change from glutamine to arginine located toward the central region of the sequence. The size of the ER protein predicted from the 589 amino acids is approximately 66,000 which fits well with the range of molecular weights previously published for the calf uterine and human ER (65,000-70,000). We observed the size of the chicken ER mRNA to be approximately 7.8 kilobases which is in agreement with the previously published size of 7.5 kilobases. In vivo secondary stimulation of chicken oviduct total RNA with diethylstilbestrol does not induce chicken ER mRNA. A time course following the chicken ER mRNA levels after secondary stimulation with diethylstilbestrol indicated a decrease in mRNA levels 8 h after DES administration. A similar study was performed using progesterone for the secondary stimulation. An increase in the chicken ER mRNA levels was observed 24 h after stimulation with progesterone. Two regions of very high homology were delineated by analyzing the sequence of this chicken ER cDNA and comparing it to the sequences of the human ER, human glucocorticoid, and chicken progesterone receptors and the P75-erbA fusion product of the avian erythroblastosis virus. The first concensus region is 72 amino acids in length and the second region of high homology is 62 amino acids long. Detailed comparisons of these regions for the steroid hormone receptors and v-erb A are presented. Possible functions for the individual regions of high homology are discussed.
Mol Endocrinol 1987 Jan
PMID:Structural organization and regulation of the chicken estrogen receptor. 290 Oct 32

Estrogen has been shown to increase proenkephalin (PE) mRNA levels in neurons of the ventrolateral aspect of the ventromedial hypothalamic nucleus (VL-VM). In this series of experiments, we examined the temporal qualities of this induction by determining both the latency of the estrogen-induced elevation in PE mRNA levels and the rate at which the message levels decline following removal of estrogen. In addition we have examined the effects of progesterone on PE gene expression in the VL-VM of estrogen-primed rats. The latency of the estrogen-induced elevation in PE mRNA levels was found to be relatively short: PE mRNA levels were increased 2-fold within 1 h of estrogen replacement. Following estrogen removal the levels of PE mRNA declined rapidly. Progesterone treatment attenuated this decline, prolonging the estrogen-induced elevation of PE mRNA levels. These results suggest that estrogen rapidly increases PE mRNA levels through a mechanism that probably involves alterations in both the rate of appearance and the rate of degradation of the message. Together, the short latency of the estrogen-induced elevation and the rapid rate of decay following estrogen removal indicate that PE gene expression is highly sensitive to fluctuating estrogen levels. The effect of progesterone suggests that this enkephalinergic system may be regulated by both estrogen and progesterone during the estrous cycle.
Brain Res Mol Brain Res 1989 Jan
PMID:Estrogen regulation of proenkephalin gene expression in the ventromedial hypothalamus of the rat: temporal qualities and synergism with progesterone. 292 83

We have examined the validity of using fluorine-substituted estrogens as probes to assess the significance of 2- and 4-hydroxylation in estrogen-induced carcinogenesis in the hamster. Liver microsomes from castrated hamsters were incubated with 2-fluoro-, 4-fluoro-, or 2,4-difluoroestradiols and analogous bromo-substituted estradiols to determine the extent of 2- and 4-hydroxylation with these substrates. Estrogen 2- and 4-hydroxylase activity was determined by radioenzymatic assay, and the 3H-labeled monomethyl ether products were identified by high performance liquid chromatography. With unsubstituted 17 beta-estradiol as substrate, 97% of the product formed was 2-hydroxylated, and 3% was 4-hydroxylated. The monosubstituted fluoroestradiols exhibited more than a 2-fold enhanced ability to form catechol estrogens compared with their corresponding bromoestradiols. Data presented herein indicate substantial defluorination when 2-fluoroestradiol was the substrate, which amounted to 36% of the total product formed, and 32% of the rate of 2-hydroxylation found with unsubstituted 17 beta-estradiol as substrate. Interestingly, the rate of 4-hydroxylation was elevated 20- and 6.7-fold, respectively, when 2-fluoroestradiol and 2,4-difluoroestradiol were the substrates compared to the rate with 17 beta-estradiol. Moreover, both 4-fluoroestradiol and 2,4-difluoroestradiol exhibited at least a 1.6-fold greater rate of 2-hydroxylation compared with 17 beta-estradiol. In contrast, the rate of dehalogenation with 2-bromoestradiol was only 12% of that found with 2-fluoroestradiol. No debromination was obtained with 4-bromoestradiol, and essentially no catechols were formed using 2,4-dibromoestradiol as substrate with these hamster liver microsomes. These data clearly provide evidence for defluorination of these substituted estrogens, particularly at the C-2 position, and seriously hamper the use of fluoroestrogens in studies of hormonal carcinogenicity.
Mol Pharmacol 1985 May
PMID:Catechol formation of fluoro- and bromo-substituted estradiols by hamster liver microsomes. Evidence for dehalogenation. 298 51

We demonstrate here the presence of two classes of EGF (epidermal growth factor) binding sites in primary cultures of male Xenopus liver parenchymal cells. One of these corresponds to the high-affinity receptor described in other tissues and species, and which exhibits the property of autophosphorylation. The number of EGF receptors decreased sharply in freshly prepared cultures but recovered to maximum levels within 24 h thereafter. Addition of EGF and insulin to the hepatocyte cultures enhanced the rate of DNA synthesis as measured by the incorporation of [3H]thymidine. Estrogen abolished this increase, reducing the incorporation to that seen with hydroxyurea. At the same time, the addition of estradiol reduced the number or activity of EGF receptors in a dose-dependent manner. The latter paralleled the activation of transcription of vitellogenin genes in Xenopus hepatocytes so that a high rate of DNA synthesis is unnecessary for or incompatible with the activation of the steroid hormone-induced vitellogenin genes.
Mol Cell Endocrinol 1985 May
PMID:Inhibition by estradiol of binding and mitogenic effect of epidermal growth factor in primary cultures of Xenopus hepatocytes. 298 31

Rat hepatic prolactin receptor is regulated by sex steroids. A high level of the receptor was found in female rats but the level was nearly undetectable in males. Gonadectomy reduced the receptor level in females but increased the level in males. Administration of estradiol benzoate (0.05 mumoles/kg on alternate days subcutaneously for 9 days) to adult gonadectomized females increased the receptor level by 473% whereas the same treatment in adult gonadectomized males produced a more modest 276% increase. This sexually dimorphic pattern in the responsiveness to estrogen stimulation in adult rats appeared to be determined neonatally. Neonatal gonadectomy of male rats changed the hepatic response system to a more female pattern in adulthood. Replacement of testosterone (1.45 mumoles at days 1 and 3 after birth) to these neonatally gonadectomized male rats restored the male pattern. Diethylstilbestrol replacement (1.45 mumoles at days 1 and 3 after birth) to the neonatally gonadectomized male rats showed the same effect as neonatally administered testosterone. Scatchard analysis revealed that the observed changes in binding are related to changes in binding capacity but not affinity. Desaturation by 4 M MgCl2 indicated that the amount of endogenously bound hormone was negligible in our membrane preparations.
Mol Cell Endocrinol 1985 May
PMID:Prolactin receptor in rat liver: sex difference in estrogenic stimulation and imprinting of the responsiveness to estrogen by neonatal androgen in male rats. 298 35

It has been shown that treatment of many but not all tumor cell lines with retinoids affects cell proliferation and expression of the transformed phenotype. To determine whether the response of the tumor cell to retinoids is influenced by specific oncogenes activated in the cell, we studied the action of these agents in the immortal, nontumorigenic Syrian hamster embryo cell lines DES-4 and 10W transfected with either v-Ha-ras or v-src oncogenes. In this paper we show that in transformed DES-4 cells expressing v-src, retinoic acid inhibited anchorage-independent growth, reduced saturation density, and inhibited the induction of ornithine decarboxylase by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. In contrast, retinoic acid enhances the expression of the transformed phenotype in DES-4-derived cells that express v-Ha-ras. In these cells retinoic acid increases the number and the average size of colonies formed in soft agar. Moreover, retinoic acid enhances ornithine decarboxylase activity and acts in a synergistic fashion with 12-O-tetradecanoylphorbol-13-acetate. These results indicate that oncogenes activated in cells can indeed influence the response of cells to retinoids. Retinoic acid does not appear to alter the levels of pp60src or p21ras proteins in these cells, suggesting that retinoic acid does not affect the synthesis of these oncogene products. Furthermore, retinoic acid does not affect the protein kinase activity of pp60src. Transformed cell lines derived from 10W cells responded differently, indicating that the presence of a specific oncogene is not the only factor determining the response to retinoids. Possible mechanisms by which retinoic acid may interfere with the expression of the oncogene products are discussed.
Mol Cell Biol 1986 Oct
PMID:Differential response to retinoic acid of Syrian hamster embryo fibroblasts expressing v-src or v-Ha-ras oncogenes. 302 89

Uterine tissue isolated from immature rats at different times after estradiol injection was incubated with medium containing [3H]lysine. The acid-extractable protein from the uterine tissue was subjected to electrophoresis on sodium dodecyl sulfate and acid-urea-Triton X-100 polyacrylamide gels, and the rate of chromatin protein synthesis determined by densitometric analysis of the fluorographs of the gels. Synthesis of chromatin proteins (histones and high mobility group chromatin proteins) was stimulated by 3 h after estrogen treatment and reached a peak at 9 h, several hours before DNA synthesis was stimulated. Synthesis of chromatin proteins occurred at the same time as total cellular protein synthesis. Estrogen stimulated the synthesis of histone variants at different rates, but the accumulation of histone proteins remained coordinated such that equivalent amounts of histone proteins were being produced at any one time.
Mol Endocrinol 1988 Aug
PMID:Differential stimulation of histone and high mobility group chromatin protein synthesis in the rat uterus by estrogen. 314 14

Estrogen stimulates DNA synthesis and cell proliferation in the luminal and glandular epithelia of rodent uterus. We tested the hypothesis that the mitogenic effect of estrogen occurs via activation of the expression of cellular proto-oncogenes by measuring the rate of transcription of 20 proto-oncogenes (abl, bas, erb-A, erb-B, ets, fms, fos, fps/fes, mos, myb, myc, N-myc, raf, Ha-ras, Ki-ras, N-ras, rel, sis, src, and B-lym) in the uterus of ovariectomized rats before and after injection of estrogen. c-onc transcriptional activity was monitored both by an in vitro transcription assay on isolated nuclei (run-on) and by analysis of mature mRNA. c-fos and c-myc proto-oncogenes were found to respond to estrogen with increased expression: c-fos within 30 min, with a first, sharp peak at 2 h and c-myc within 1.5 h, with a first, broad peak at 4-6 h. DNA synthesis start to increase in the uterus 13 h after estrogen injection and show a first peak at 24 h. In the liver and muscle of the same animals there is neither elevation of c-fos and c-myc expression nor increase of DNA synthesis. The kinetics of the induction by estrogen of c-fos gene expression in the uterus parallels the rate of formation of active nuclear estrogen-receptor complex. Furthermore, the ability of estrogen to induce c-fos mRNA was not abolished by the protein synthesis inhibitor cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1988 Sep
PMID:Estrogen induces expression of c-fos and c-myc protooncogenes in rat uterus. 317 52

The effect of chronic estrogen treatment on the stimulation and dopamine inhibition of anterior pituitary (AP) adenylate cyclase (AC) activity was examined. Treatment of ovariectomized female rats with estradiol for 21 days resulted in a 450% increase in AP weight compared to ovariectomized controls. Stimulation of AC by guanine nucleotides (GN) (1 nM-0.1 mM) and vasoactive intestinal peptide (1 microM) was reduced by 50%. Stimulation of AC by fluoride ions was unchanged by estradiol treatment. Stimulation above basal by forskolin was reduced by variable amounts (23-50%), and depended on the concentration of forskolin used. Inhibition of AC mediated by D2-dopamine receptors was decreased by 45%. Estrogen treatment had no effect on the toxin-catalyzed incorporation of [32P]ADP into stimulatory and inhibitory GN regulatory proteins. These results indicate that the effect of estrogen on the anterior pituitary include modulation of stimulated, dopamine-inhibited and basal AC activity.
Mol Cell Endocrinol 1988 Sep
PMID:Estrogen regulation of rat anterior pituitary adenylate cyclase. 319 19

The role of estradiol in the regulation of its cognate receptor in MCF-7 cells was investigated in this study. After treatment with 10(-9) M estradiol, the level of receptor protein was measured using an enzymeimmunoassay. By 6 h, the receptor protein declined by about 60% from a level of approximately 3.6 to 1.2 fmol/micrograms DNA. The level of receptor remained suppressed for 24-48 h. Similar results were obtained with an estrogen receptor (ER) binding assay. The steady state level of ER mRNA was determined by an RNase protection assay. Estrogen treatment resulted in a maximum suppression of mRNA by 6 h. Receptor mRNA remained depressed for 48 h. Transcription run on experiments demonstrated a transient decrease of about 90% in ER transcription after 1 h. By 3-6 h transcription increased approximately 2-fold and remained elevated for at least 48 h. These data suggest that estrogen down-regulates ER mRNA by inhibition of ER gene transcription at early times and by a posttranscriptional effect on receptor mRNA at later times.
Mol Endocrinol 1988 Dec
PMID:Regulation of the estrogen receptor in MCF-7 cells by estradiol. 321 58


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