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1.
Although estrogen action is indispensable for normal bone growth in both genders, the roles of estrogen receptors (ERs) in
mediating bone growth are not fully understood. The effects of ER inactivation on bone growth are sex and age dependent, and
may differ between the axial and appendicular regions. In this study, the spatial and temporal expression of ERα and β in
the tibial and spinal growth plates of the female and male rats during postnatal development was examined to explore the possible
mechanisms. The level of mRNA was examined and compared with quantitative real-time PCR. The spatial location was determined
by immunohistochemical analysis. The 1-, 4-, 7-, 12- and 16-week age stages correspond to early life, puberty and early adulthood
after puberty, respectively. Gender- and region-specific differences in ERα and β expression were shown in the growth plates.
Mainly nuclear staining of ERα and β immunoreactivity was demonstrated in the spinal and tibial growth plate chondrocytes
for both genders. Moreover, our study indicated significant effect of gender on temporal ERα and β expression and of region
on temporal ERα/ERβ expression ratio. However, spatial differences of region-related ERα and β expression were not observed.
Gender-related spatial changes were detected only at 16 weeks of both spine and limb growth plates. ERα and β immunoreactivity
was detected in the resting, proliferative and prehypertrophic chondrocytes in the early life stage and during puberty. After
puberty, ERα expression was mainly located in the late proliferative and hypertrophic chondrocytes in female, whereas the
expression still extended from the resting to hypertrophic chondrocytes in males. Gender- and region-specific expression patterns
of ERα and β gene might be one possible reason for differences in sex- and region-related body growth phenotypes. Gender,
age and region differences should be taken into consideration when the roles of ERs in the growth plate are investigated. 相似文献
2.
3D-QSAR and molecular docking analysis were performed to explore the interaction of estrogen receptors (ERα and ERβ) with
a series of 3-arylquinazolinethione derivatives. Using the conformations of these compounds revealed by molecular docking,
CoMFA analysis resulted in the first quantitative structure-activity relationship (QSAR) and first quantitative structure-selectivity
relationship (QSSR) models predicting the inhibitory activity against ERβ and the selectivity against ERá. The q2 and R2 values, along with further testing, indicate that the obtained 3D-QSAR and 3D-QSSR models will be valuable in predicting
both the inhibitory activity and selectivity of 3-arylquinazolinethione derivatives for these protein targets. A set of 3D
contour plots drawn based on the 3D-QSAR and 3D-QSSR models reveal modifications of substituents at C2 and C5 of the quinazoline
which my be useful to improve both the activity and selectivity of ERβ/ ERα. Results showed that both the steric and electrostatic
factors should appropriately be taken into account in future rational design and development of more active and more selective
ERβ inhibitors for the therapeutic treatment of osteoporosis.
Figure Structures of ERβ binding with compounds 1aar, 1ax and 1aag obtained from molecular docking 相似文献
3.
Since the estrogen receptor α (ERα) and β (ERβ) are thought to mediate different biological effects, there is intense interest
in designing or screening subtype-selective ER ligands. Here, we constructed a biosensor identified as bipartite recombinant
yeast system (BRYS) to screen and evaluate subtype-selective ER ligands. Uniform design and immunoblotting was used to determine
an optimal dose of copper which control the expression of ERs through a copper inducible metallothionine promoter (CUP1).
Some chemicals including natural estrogen (17β-estradiol), specific estrogen receptor agonist (PPT and DPN), and phytoestrogens
(genistein) were tested to validate this system. There was obvious and anticipative discrimination between the agonistic activities
when these chemicals were identified and characterized. Furthermore, antagonist (ICI 182,780), which could antagonize the
transactivation of estrogen, and chromatin immunoprecipitation (ChIP) were used to confirm that the agonistic effects were
mediated through ERs. Comparative studies showed that this system was reproducible and sensitive. 4.7 pM (1.3 ng/l) estrogen
was the lowest concentration that could be detected to ERα and 0.12 nM (33.5 ng/l) for ERβ. The results from our study showed
that in vitro screening for subtype-selective ER ligands could be conducted in a simple yeast system that is rapid, sensitive,
reliable, and quantitative.
An erratum to this article can be found at 相似文献
4.
This study was designed to determine the expression pattern of estrogen receptor (ER) subtypes in the Acomys cahirinus ovarian cells during its postnatal development.
Immunohistochemical studies revealed the presence of ERα and ERβ in germinal epithelium cells and interstitial tissue. Both
these ER subtypes were also seen in granulosa cells and oocytes of growing follicles, however, the level of ERβ expression
was higher in comparison with ERα. In contrast to ERβ, ERα protein was also present in theca cells.
The expression of ERs increased with animals’ age, but it decreased during follicular maturation. Moreover, the immunolocalization
of ER subtypes in luteal cells showed that not ERβ, but ERα expression is up-regulated throughout corpus luteum development.
These immunohistochemical studies demonstrate, for the first time, that ERα is also expressed in the mouse granulosa cells
and it may be a mediator of estrogen action in granulosa cells proliferation and differentiation. 相似文献
5.
Cimarosti H O'Shea RD Jones NM Horn AP Simão F Zamin LL Nassif M Frozza R Netto CA Beart PM Salbego C 《Neurochemical research》2006,31(4):483-490
The molecular basis of estrogen-mediated neuroprotection against brain ischemia remains unclear. In the present study, we investigated changes in expression of estrogen receptors (ERs) α and β and excitatory amino acid transporters (EAAT) 1 and 2 in rat organotypic hippocampal slice cultures treated with estradiol and subsequently exposed to oxygen--glucose deprivation (OGD). Pretreatment with 17β-estradiol (10 nM) for 7 days protected the CA1 area of hippocampus against OGD (60 min), reducing cellular injury by 46% compared to the vehicle control group. Levels of ERα protein were significantly reduced by 20% after OGD in both vehicle- and estradiol-treated cultures, whereas ERβ was significantly up-regulated by 25% in the estradiol-treated cultures. In contrast, EAAT1 and EAAT2 levels were unchanged in response to estradiol treatment in this model of OGD. These findings suggest that estrogen-induced neuroprotection against ischemia might involve regulation of ERβ and, consequently, of the genes influenced by this receptor.Helena Cimarosti and Ross D. O’Shea, equal first authors. 相似文献
6.
7.
The aims of the present study were to detect the ontogeny of estrogen receptor (ERα and ERβ) and androgen receptor (AR) expressions
and their co-localization with Islet-1 in the developing dorsal root ganglia (DRG) of sheep fetuses by immunohistochemistry.
From the single staining results, the ERα immunoreactivity (ERα-ir), ERβ immunoreactivity (ERβ-ir) and AR immunoreactivity
(AR-ir) was first detected at days 90, 120 and 90 of gestation, respectively. From days 90 to 120, ERα and AR were consistently
detected in the nuclei of DRG neurons and the relative percentage (approximately 60%) of ERα-ir or AR-ir cells did not change
significantly. Moreover, there was no change in ERα expression, while a dramatic loss of AR expression was observed at birth.
From day 120 of gestation to birth, very few neurons (approximately 8%) showed nuclear ERβ immunoreactivity. The dual staining
results showed that Islet-1 was co-localized with ERα, ERβ or AR in the nuclei of DRG neurons with various frequencies, and
over 70% ERα-ir, ERβ-ir or AR-ir cells contained Islet-1. These results imply that ERs, AR and Islet-1 may be important in
regulating the differentiation and functional maintenance of some phenotypes of DRG neurons after mid-gestation in the sheep
fetus. 相似文献
8.
9.
10.
Hua Zhu Liliang Huang Yuanqing Zhang Xiaoping Xu Yanhong Sun Yu-Mei Shen 《Journal of biological inorganic chemistry》2010,15(4):591-599
To develop technetium- and rhenium-labeled nonsteroidal estrogen imaging agents for estrogen receptor (ER) positive breast
tumors, two groups of rhenium and technetium cyclofenil derivatives were synthesized and characterized. The binding affinities
of the rhenium complexes for ERs were determined. The tricarbonyl rhenium complex showed the highest binding affinity for
ERs (81.2 for ERβ, 16.5 for ERα). Tricarbonyl technetium cyclofenil complexes were obtained in high radiochemical purity and
radiochemical yields. The results of studies of their octanol/water partition and in vitro stability are presented. These
results demonstrate that these radiolabeled cyclofenil derivatives may be considered as potential breast cancer imaging agents. 相似文献
11.
Bogush TA Dudko EA Beme AA Bogush EA Kim AI Polotsky BE Tjuljandin SA Davydov MI 《Biochemistry. Biokhimii?a》2010,75(12):1421-1427
This review considers data on expression of different types of estrogen receptors (ERα and ERβ) in in vitro cultured cells of non-small cell lung cancer and also in human and animal lung tumors. Estrogens are shown to play an important
role in genesis and development of non-small cell lung cancer because the estrogen-stimulated cell proliferation as well as
antiestrogen-caused inhibition of proliferation occurred only in the cells expressing different types of estrogen receptors.
In general, the situation is similar to that observed in breast cancer, but in the cells of non-small cell lung cancer not
ERα are expressed in more than half of cases but ERβ. Just estrogen receptors β play the crucial role in inducing cell proliferation
in response to estrogens, and ERβ is a prognostic marker of a favorable course of non-small cell lung cancer. Data on the
interactions between ER and EGFR signaling pathways, as well as on the additive antitumor effect of antiestrogens (tamoxifen
and fulvestrant) combined with tyrosine kinase inhibitors (gefitinib, erlotinib, and vandetanib) are considered. The review
also includes data on the influence of estrogens on genesis and development of lung cancer in humans and animals and the frequency
of ERα and ERβ expression in non-small cell lung cancer in tissues from patients of the two sexes. Problems of quantitative
determination of α and β estrogen receptors in the tumor cells are also discussed. 相似文献
12.
Pavlik R Wypior G Hecht S Papadopoulos P Kupka M Thaler C Wiest I Pestka A Friese K Jeschke U 《Histochemistry and cell biology》2011,136(3):289-299
Estradiol and progesterone mediate their actions by binding to classical nuclear receptors, estrogen receptor α (ERα) and
estrogen receptor β (ERβ) and progesterone receptor A and B (PR-A and PR-B) and the non-classical G protein-coupled estrogen
receptor (GPER). Several animal knock-out models have shown the importance of the receptors for growth of the oocyte and ovulation.
The aim of our study was to identify GPER in human granulosa cells (GC) for the first time. Moreover, the effect of different
doses of gonadotropins on estrogen and progesterone receptors in the human ovary should be investigated as follicle stimulating
hormone (FSH) and luteinizing hormone (LH) are also responsible for numerous mechanisms in the ovary like induction of the
steroid biosynthesis. Human GC were cultured in vitro and stimulated with different doses of recombinant human FSH or LH.
Receptor expression was analyzed by immunocytochemistry and quantitative real-time RT-PCR. GPER could be identified for the
first time in human GC. It could be shown that high concentrations of LH increase GPER protein expression. Furthermore FSH
and LH increased ERβ, PR-A and PR-B significantly on protein level. These findings were verified for high doses of FSH and
LH on mRNA level. ERα was not affected with FSH or LH. We assume that gonadotropins induce GPER, ERβ and PR in luteinized
granulosa cells. 相似文献
13.
Considerable effort by numerous laboratories has resulted in an improved understanding of estrogen and SERM action mediated by the two estrogen receptors, ERα and ERβ. However, many of the targets for ERβ in cell physiology remain elusive. Here, the C4-12/Flag.ERβ cell line which stably expressed Flag.ERβ is used to study ERβ genomic functions without ERα interference. Mapping ERβ binding sites in these cells reveals ERβ unique distribution and motif enrichment patterns. Accompanying our mapping results, nascent RNA profiling is performed on cells at the same treatment time. The combined results allow the identification of ERβ target genes. Gene ontology analysis reveals that ERβ targets are enriched in differentiation, development and apoptosis. Concurrently, E2 treatment suppresses proliferation in these cells. Within ERβ binding sites, while the most prevalent binding motif is the canonical ERE, motifs of known ER interactors are also enriched in ERβ binding sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1, which are unique to ERβ binding sites in these cells. Further characterization confirms the association between EBF1 and the estrogen receptors, which favors the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs at the protein level. In summary, by studying ERβ genomic functions in our cell model, we confirm the anti-proliferative role of ERβ and discover the novel cross talk of ERβ with EBF1 which has various implications in normal physiology. 相似文献
14.
Shukuwa K Izumi S Hishikawa Y Ejima K Inoue S Muramatsu M Ouchi Y Kitaoka T Koji T 《Histochemistry and cell biology》2006,126(1):111-123
Diethylstilbestrol (DES) has been implicated in mammalian abnormalities. We examined the effects of DES on follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) cells in the pituitaries of male mice treated with various doses of DES for 20 days. DES reduced the density of FSH and LH cells in a dose-dependent manner, but increased that of PRL cells. When the expression of estrogen receptor (ER) α and β was assessed, an induction of ERβ by DES was found predominantly in PRL cells. However, since these effects were abolished in ERα knockout mice, DES appears to act primarily through ERα. When the expression of Ki-67 and Pit-1 in PRL cells was examined at various time-points after DES treatment, some PRL cells became Ki-67 positive at 10–15 days, and Pit-1-positive cells were increased at 5–15 days. Furthermore, some FSH and LH cells became Pit-1 positive, and co-localized with PRL at 5–10 days. Our results indicate that DES increases PRL cells by inducing proliferation of PRL cells and transdifferentiation of FSH/LH cells to PRL cells. 相似文献
15.
Lekhkota O Brehm R Claus R Wagner A Bohle RM Bergmann M 《Histochemistry and cell biology》2006,125(3):259-264
Boar testes synthesize high amounts of estrogens which are known to stimulate several male sexual functions in a variety of
extragonadal target tissues. Possible effects within the testis depend on the existence of the estrogen receptor subtypes
α and β (ERα, ERβ). The precise cellular localization of these subtypes within the testis was, so far, based mainly on protein
expression studies using different antibodies in several species including boars shows contradictory results. Therefore, we
investigated the ERα and ERβ gene expression using RT-PCR of testis homogenates and RT-PCR after UV-single cell microdissection
combined with in-situ hybridization of four fertile boars with an average age of 32 weeks. Both ERα and ERβ mRNA were found
in testis homogenates. Using in-situ hybridization and UV-single cell microdissection ERα mRNA was present in type A and type
B spermatogonia up to mid-pachytene primary spermatocytes in stage V–VIII and stage I of the seminiferous epithelial cycle,
but not in other cells. ERβ mRNA was found only in Sertoli cells. Interstitial Leydig cells revealed neither ERα nor ERβ mRNA.
The data suggest a direct impact of estrogen in the boar on Sertoli cell function via ERβ and germ cell formation via ERα. 相似文献
16.
Oestrogen receptor β is present in both muscle fibres and endothelial cells within human skeletal muscle tissue 总被引:1,自引:1,他引:0
Wiik A Ekman M Morgan G Johansson O Jansson E Esbjörnsson M 《Histochemistry and cell biology》2005,124(2):161-165
Oestrogen receptor β (ERβ) is expressed in human skeletal muscle tissue. In the present study, we have developed an immunohistochemical
method to reveal if ERβ is located within the muscle fibres as well as within capillaries. Skeletal muscle biopsies were obtained
from m. quadriceps femoris vastus lateralis in four healthy young subjects. Immunohistochemical triple staining was applied
to transverse sections of paraffin-wax-embedded tissue. The basement membrane of muscle fibres and capillaries was identified
by using an antibody to collagen IV, endothelial cells using an antibody to CD34 and ERβ using a corresponding antibody. The
ERβ-positive (ERβ+) nuclei were located within the muscle fibre defined by the localisation of collagen IV. ERβ+ nuclei were
also, for the first time, found in endothelial cells of capillaries in skeletal muscle tissue. Quantification was performed
on transverse cryostat sections after performing a double staining (collagen IV and ERβ). It was shown that 24% of the ERβ+
nuclei were located within capillaries, and 76% were located within muscle fibres. In conclusion, ERβ in human skeletal muscle
tissue is expressed not only in the muscle fibres themselves, but also within the capillary endothelial cells. This observation
might improve understanding of the physiological role of oestrogen and its receptor. 相似文献
17.
The production of estrogen receptors (ER) in cultured insect cells is advantageous because these cells are relatively easy
to culture and they perform post-translation modifications necessary for protein stability and function. There are three options
for protein expression in insect cells: transient transfection, lytic baculovirus infection, or transfection followed by selection
to create stable cell lines. Stable transfection has been promoted to be advantageous for the production of recombinant proteins
because no re-infection is required, which might provide better lot-to-lot reproducibility in protein production. In this
paper, we demonstrate that lytic baculovirus infection of Sf21 cells yields approximately tenfold more bioactive ERβ than
cells stably transformed with pIZ/V5-His plasmid under OpIE2 promoter. We provide the first evidence that stable expression
of recombinant human ERβ decreases the proliferation of Sf21 cells by inhibition of cell replication in a ligand-independent
manner. These results mirror findings in breast cancer cells showing that an increase in ERβ expression decreases cell proliferation.
We conclude that baculovirus infection of Sf21 cells is better for human ERβ production than stable-transformation of Sf21
cells. 相似文献
18.
19.
The brain undergoes many structural and functional changes during aging. Some of these changes are regulated by estrogens which act mainly through their intracellular receptors, estrogen receptor ERα and ERβ. The expression of these receptors is regulated by several factors including their own ligand estrogen, and others such as growth hormone and thyroid hormone. The levels of these factors decrease during aging which in turn influence estrogen signaling leading to alterations in brain functions. In the present paper, we review the effects of aging on brain structure and function, and estrogen action and signaling during brain aging. The findings suggest key role of estrogen in the maintenance of brain functions during aging. 相似文献
20.
Zahra Moinfar Hannes Dambach Bodo Schoenebeck Eckart F?rster Nora Prochnow Pedro Michael Faustmann 《PloS one》2016,11(2)