scholarly journals Different regions of the estrogen receptor are required for synergistic action with the glucocorticoid and progesterone receptors.

1989 ◽  
Vol 9 (12) ◽  
pp. 5324-5330 ◽  
Author(s):  
A C Cato ◽  
H Ponta
Keyword(s):  
Estrogen Receptor ◽  
Glucocorticoid Receptor ◽  
Binding Sites ◽  
Glucocorticoid Receptors ◽  
Steroid Receptors ◽  
Gene Activation ◽  
Synergistic Action ◽  
Receptor Expression ◽  
Expression Vectors ◽  
Mutant Receptor

Estrogen and progesterone or estrogen and glucocorticoid receptors functionally cooperate in gene activation if their cognate binding sites are close to one another. These interactions have been described as synergism of action of the steroid receptors. The mechanism by which synergism is achieved is not clear, although protein-protein interaction of the receptors is one of the favorite models. In transfection experiments with receptor expression vectors and a reporter gene containing estrogen and progesterone-glucocorticoid receptor binding sites, we have examined the effects that different portions of the various receptors have on synergism. N-terminal domains of the chicken progesterone and human glucocorticoid receptors, when deleted, abolished the synergistic action of these receptors with the estrogen receptor. Deletion of the carboxy-terminal amino acids 341 to 595 of the estrogen receptor produced a mutant receptor that could not trans-activate on its own. This mutant receptor did not affect the action of the glucocorticoid receptor but functioned synergistically with the progesterone receptor. We therefore conclude that the synergistic action of the receptors for estrogen and progesterone is mechanistically different from the synergistic action of the receptors for estrogen and glucocorticoid.

Different regions of the estrogen receptor are required for synergistic action with the glucocorticoid and progesterone receptors

1989 ◽  
Vol 9 (12) ◽  
pp. 5324-5330
Author(s):  
A C Cato ◽  
H Ponta
Keyword(s):  
Estrogen Receptor ◽  
Glucocorticoid Receptor ◽  
Binding Sites ◽  
Glucocorticoid Receptors ◽  
Steroid Receptors ◽  
Gene Activation ◽  
Synergistic Action ◽  
Receptor Expression ◽  
Expression Vectors ◽  
Mutant Receptor

Estrogen and progesterone or estrogen and glucocorticoid receptors functionally cooperate in gene activation if their cognate binding sites are close to one another. These interactions have been described as synergism of action of the steroid receptors. The mechanism by which synergism is achieved is not clear, although protein-protein interaction of the receptors is one of the favorite models. In transfection experiments with receptor expression vectors and a reporter gene containing estrogen and progesterone-glucocorticoid receptor binding sites, we have examined the effects that different portions of the various receptors have on synergism. N-terminal domains of the chicken progesterone and human glucocorticoid receptors, when deleted, abolished the synergistic action of these receptors with the estrogen receptor. Deletion of the carboxy-terminal amino acids 341 to 595 of the estrogen receptor produced a mutant receptor that could not trans-activate on its own. This mutant receptor did not affect the action of the glucocorticoid receptor but functioned synergistically with the progesterone receptor. We therefore conclude that the synergistic action of the receptors for estrogen and progesterone is mechanistically different from the synergistic action of the receptors for estrogen and glucocorticoid.

scholarly journals Gene activation and repression by the glucocorticoid receptor are mediated by sequestering Ep300 and two modes of chromatin binding

2019 ◽  
Author(s):  
Avital Sarusi Portuguez ◽  
Ivana Grbesa ◽  
Moran Tal ◽  
Rachel Deitch ◽  
Dana Raz ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Binding Sites ◽  
Gene Activation ◽  
Spatial Separation ◽  
Regulatory Elements ◽  
Chromatin Interaction ◽  
Chromatin Binding ◽  
Physiological Processes ◽  
Regulatory Loci ◽  
Open Question

ABSTRACTThe transcription factor glucocorticoid receptor (GR) is a key mediator of stress response and a broad range of physiological processes. How can GR rapidly activate the expression of some genes while repress others, remains an open question due to the challenge to associate GR binding sites (GBSs) to their distant gene targets. Mapping the full 3D scope of GR-responsive promoters using high-resolution 4C-seq unravelled spatial separation between chromatin interaction networks of GR-activated and repressed genes. Analysing GR binding sites and other regulatory loci in their functional 3D context revealed that GR sequesters the co-activator Ep300 from active non-GBS enhancers in both activated and repressed gene compartments. While this is sufficient for rapid gene repression, gene activation is countered by productive recruitment of Ep300 to GBS. Importantly, in GR-activated compartments Klf4 binding at non-GBS regulatory elements cluster in 3D with GBS and antagonizes GR activation. In addition, we revealed ROR and Rev-erb transcription factors as novel co-regulators for GR-mediated gene expression.

scholarly journals Estrogen Receptor, Progesterone Receptor and Glucocorticoid Receptor Expression in Normal Myometrium and in Leomyoma

2017 ◽  
Vol 1 (2) ◽  
Keyword(s):  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Glucocorticoid Receptor ◽  
Uterine Leiomyoma ◽  
Receptor Expression ◽  
Therapeutic Action ◽  
Estrogen Sulfotransferase ◽  
Smooth Muscle Tumour ◽  
Significant Difference ◽  
Expression Status

Uterine leiomyoma is the most common benign smooth muscle tumour that originates from the myometrium. Ovarian sex steroids are responsible for the growth of such tumours, though estrogen and progesterone are not the only modulators involved in the tumourigenesis and growth of leiomyomata. The activation of glucocorticoid receptor (GR) can induce the expression and activity of estrogen sulfotransferase, an enzyme that generally inactivates estrogen, because of the effects of sulfonated estrogen fails to activate the estrogen receptor, it is of interest to know whether GR is present or not in leiomyomata and in the normal myometrium. The aim of this study is to analyse the expression of GR in leiemyoma and myometrium. Method: The immunohistochemistry of 47 patients was tested to find the expression status of estrogen receptor (ER), progesterone receptor (PR) and GR in leiemyoma and normal myometrium. Results: GR, ER and PR were expressed in both normal myometrium and in leiomyoma. There was a significant difference in the expression of GR found in normal myometrium compared with those expressed in leiomyoma (Allred Score, 256±29 versus 91 ±23). The GR expressed was significantly lower than the ER and PR expressed in leiomyoma. Conclusion: This presence of GR in the normal myometrium and in myomas is interesting and could be used for therapeutic action. But, first, the roles of G on myomas have to be understand.

scholarly journals Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and glucocorticoid receptors.

1990 ◽  
Vol 1 (3) ◽  
pp. 291-299 ◽  
Author(s):  
D Picard ◽  
V Kumar ◽  
P Chambon ◽  
K R Yamamoto
Keyword(s):  
Signal Transduction ◽  
Estrogen Receptor ◽  
Glucocorticoid Receptor ◽  
Nuclear Localization ◽  
Glucocorticoid Receptors ◽  
Common Mechanism ◽  
Hormone Binding ◽  
Nuclear Localization Signals ◽  
Binding Regions ◽  
Human Estrogen Receptor

The glucocorticoid receptor accumulates in nuclei only in the presence of bound hormone, whereas the estrogen receptor has been reported to be constitutively nuclear. To investigate this distinction, we compared the nuclear localization domains of the two receptors and the capacity of their respective hormone-binding regions to regulate nuclear localization activity. As with the glucocorticoid receptor, we showed that the human estrogen receptor contained a nuclear localization signal between the DNA-binding and hormone-binding regions (amino acids 256-303); however, in contrast to the glucocorticoid receptor, the estrogen receptor lacked a second nuclear localization domain within the hormone-binding region. Moreover, the hormone-binding domain of the unliganded estrogen receptor failed to regulate nuclear localization signals, although it efficiently regulated other receptor functions. We conclude that the two receptors employ a common mechanism for signal transduction involving a novel "inactivation" function, but that they differ in their control of nuclear localization. Thus, despite the strong relatedness of the estrogen and glucocorticoid receptors in structure and activity, certain differences in their properties could have important functional implications.

scholarly journals Neonatal Exposure to Bisphenol A Alters Rat Uterine Implantation-Associated Gene Expression and Reduces the Number of Implantation Sites

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1101-1111 ◽  
Author(s):  
Jorgelina Varayoud ◽  
Jorge G. Ramos ◽  
Verónica L. Bosquiazzo ◽  
Melina Lower ◽  
Mónica Muñoz-de-Toro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Bisphenol A ◽  
Steroid Receptors ◽  
Estrogen Receptor Α ◽  
Receptor Expression ◽  
Female Rats ◽  
Postnatal Exposure ◽  
Long Term Effects ◽  
Implantation Sites

Endocrine disrupters have been associated with reproductive pathologies such as infertility and gynecological tumors. Using a rat model of early postnatal exposure to bisphenol A (BPA), we evaluated the long-term effects on 1) female reproductive performance, 2) uterine homeobox A10 (Hoxa10) and Hoxa10-target gene expression, and 3) ovarian steroid levels and uterine estrogen receptor α and progesterone (P) receptor expression. Newborn female rats received vehicle, BPA.05 (0.05 mg/kg · d), BPA20 (20 mg/kg · d), diethylstilbestrol.2 (0.2 μg/kg · d), or diethylstilbestrol 20 (20 μg/kg · d) on postnatal d 1, 3, 5, and 7. A significant decrease in the number of implantation sites was assessed in the xenoestrogen-exposed females. To address the molecular effects of postnatal xenoestrogen exposure on the pregnant uterus, we evaluated the expression of implantation-associated genes on d 5 of pregnancy (preimplantation uterus). All xenoestrogen-treated rats showed a lower expression of Hoxa10. In the same animals, two Hoxa10-downstream genes were misregulated in the uterus. β3Integrin, which is up-regulated by Hoxa10 in controls, was decreased, whereas empty spiracles homolog 2, which is down-regulated by Hoxa10, was increased. Furthermore a clear down-regulation of estrogen receptor α and P receptor expression was detected without changes in estradiol and P serum levels. The early exposure to BPA produced a lower number of implantation sites in association with a defective uterine environment during the preimplantation period. Alterations in the endocrine-regulated Hoxa10 gene pathways (steroid receptors—Hoxa10—β3integrin/empty spiracles homolog 2) could explain, at least in part, the BPA effects on the implantation process.

scholarly journals Mutational studies reveal a complex set of positive and negative control elements within the chicken vitellogenin II promoter.

1991 ◽  
Vol 11 (5) ◽  
pp. 2704-2717 ◽  
Author(s):  
S N Seal ◽  
D L Davis ◽  
J B Burch
Keyword(s):  
Estrogen Receptor ◽  
Binding Sites ◽  
Expression Vector ◽  
Negative Control ◽  
Receptor Expression ◽  
Estrogen Receptor Expression ◽  
Related Factors ◽  
Dnase I Footprinting ◽  
Lmh Cells

The endogenous chicken vitellogenin II (VTGII) gene is transcribed exclusively in hepatocytes in response to estrogen. We previously identified two estrogen response elements (EREs) upstream of this gene. We now present an analysis of the VTGII promoter activated by these EREs in response to estrogen. Chimeric VTGII-CAT genes were cotransfected into LMH chicken hepatoma cells along with an estrogen receptor expression vector, and transient CAT expression was assayed after culturing the cells in the absence or presence of estrogen. An analysis of constructs bearing deletions downstream of the more proximal ERE indicated that promoter elements relevant to transcription in LMH cells extend to between -113 and -96. The relative importance of sequences within the VTGII promoter was examined by using 10 contiguous linker scanner mutations spanning the region from -117 to -24. Although most of these mutations compromised VTGII promoter function, one dramatically increased expression in LMH cells and also rendered the VTGII promoter capable of being activated by cis-linked EREs in fibroblasts cotransfected with an estrogen receptor expression vector. Gel retardation and DNase I footprinting assays revealed four factor-binding sites within this promoter. We demonstrate that three of these sites bind C/EBP, SP1, and USF (or related factors), respectively; the fourth site binds a factor that we denote TF-V beta. The biological relevance of these findings is suggested by the fact that three of these binding sites map to sites previously shown to be occupied in vivo in response to estrogen.

scholarly journals Steroidogenic Enzyme and Steroid Receptor Expression in the Equine Accessory Sex Glands

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2322
Author(s):  
Robyn E. Ellerbrock ◽  
Giorgia Podico ◽  
Kirsten E. Scoggin ◽  
Barry A. Ball ◽  
Mariano Carossino ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Steroid Receptors ◽  
Steroid Receptor ◽  
Receptor Expression ◽  
Sex Steroid ◽  
Steroidogenic Enzymes ◽  
Steroidogenic Enzyme ◽  
Accessory Sex Glands ◽  
Sex Steroid Receptors ◽  
Steroid Receptor Expression

The expression pattern and distribution of sex steroid receptors and steroidogenic enzymes during development of the equine accessory sex glands has not previously been described. We hypothesized that equine steroidogenic enzyme and sex steroid receptor expression is dependent on reproductive status. Accessory sex glands were harvested from mature stallions, pre-pubertal colts, geldings, and fetuses. Expression of mRNA for estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), androgen receptor (AR), 3β-Hydroxysteroid dehydrogenase/Δ5-4 isomerase (3βHSD), P450,17α hydroxylase, 17–20 lyase (CYP17), and aromatase (CYP19) were quantified by RT-PCR, and protein localization of AR, ER-α, ER-β, and 3βHSD were investigated by immunohistochemistry. Expression of AR, ESR2, CYP17, or CYP19 in the ampulla was not different across reproductive statuses (p > 0.1), while expression of ESR1 was higher in the ampulla of geldings and fetuses than those of stallions or colts (p < 0.05). AR, ESR1 and ESR2 expression were decreased in stallion vesicular glands compared to the fetus or gelding, while AR, ESR1, and CYP17 expression were decreased in the bulbourethral glands compared to other glands. ESR1 expression was increased in the prostate compared to the bulbourethral glands, and no differences were seen with CYP19 or 3β-HSD. In conclusion, sex steroid receptors are expressed in all equine male accessory sex glands in all stages of life, while the steroidogenic enzymes were weakly and variably expressed.

Effect of a single treatment (imprinting) with genistein or combined treatment with genistein+benzpyrene on the binding capacity of glucocorticoid and estrogen receptors of adult rats

2002 ◽  
Vol 21 (5) ◽  
pp. 231-234 ◽  
Author(s):  
G Csaba ◽  
Á Inczefi-Gonda
Keyword(s):  
Glucocorticoid Receptor ◽  
Estrogen Receptors ◽  
Glucocorticoid Receptors ◽  
Steroid Receptors ◽  
Binding Capacity ◽  
Combined Treatment ◽  
Female Rats ◽  
Adult Rats ◽  
Male And Female Rats ◽  
Genistein Treatment

Hormonal imprinting takes place perinatally at the first encounter between the hormone and its target receptor. This is needed for the normal finishment of the maturation of the receptor–signal transduction system. In excess of foreign molecules, which can also bind to the receptor, faulty imprinting develops with life-long consequences. Genistein, a soybean phytosteroid (isoflavone), has estrogen-like effects and can be bound by steroid receptors. In the present experiments, single neonatal treatment (imprinting) with 20 m g of genistein, or combined treatment with 20 m g of genistein+20 m g of benzpyrene was done and liver and thymus glucocorticoid receptors of adult male and female rats and uterine estrogen receptors were studied. There was no difference in the binding capacity of uterine estrogen receptors. Genistein treatment alone caused a significant reduction of liver glucocorticoid receptor density in males; however, there were no other significant alterations. After combined genistein+benzpyrene treatment, more than half of the thymus and liver glucocorticoid receptor values significantly changed. The results call attention to the imprinting-modifying effect of a second (environmental) imprinter.

Mutational studies reveal a complex set of positive and negative control elements within the chicken vitellogenin II promoter

1991 ◽  
Vol 11 (5) ◽  
pp. 2704-2717
Author(s):  
S N Seal ◽  
D L Davis ◽  
J B Burch
Keyword(s):  
Estrogen Receptor ◽  
Binding Sites ◽  
Expression Vector ◽  
Negative Control ◽  
Receptor Expression ◽  
Estrogen Receptor Expression ◽  
Related Factors ◽  
Dnase I Footprinting ◽  
Lmh Cells

The endogenous chicken vitellogenin II (VTGII) gene is transcribed exclusively in hepatocytes in response to estrogen. We previously identified two estrogen response elements (EREs) upstream of this gene. We now present an analysis of the VTGII promoter activated by these EREs in response to estrogen. Chimeric VTGII-CAT genes were cotransfected into LMH chicken hepatoma cells along with an estrogen receptor expression vector, and transient CAT expression was assayed after culturing the cells in the absence or presence of estrogen. An analysis of constructs bearing deletions downstream of the more proximal ERE indicated that promoter elements relevant to transcription in LMH cells extend to between -113 and -96. The relative importance of sequences within the VTGII promoter was examined by using 10 contiguous linker scanner mutations spanning the region from -117 to -24. Although most of these mutations compromised VTGII promoter function, one dramatically increased expression in LMH cells and also rendered the VTGII promoter capable of being activated by cis-linked EREs in fibroblasts cotransfected with an estrogen receptor expression vector. Gel retardation and DNase I footprinting assays revealed four factor-binding sites within this promoter. We demonstrate that three of these sites bind C/EBP, SP1, and USF (or related factors), respectively; the fourth site binds a factor that we denote TF-V beta. The biological relevance of these findings is suggested by the fact that three of these binding sites map to sites previously shown to be occupied in vivo in response to estrogen.

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