INT173926

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Context Info
Confidence 0.27
First Reported 2003
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 21
Total Number 28
Disease Relevance 11.39
Pain Relevance 4.24

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (Atp6v1e1) endosome (Atp6v1e1) transport (Atp6v1e1)
mitochondrion (Atp6v1e1) cytoplasm (Atp6v1e1)
Anatomy Link Frequency
spine 4
capsules 3
uterine 3
neurons 2
Mammary gland 1
Atp6v1e1 (Mus musculus)
Pain Link Frequency Relevance Heat
Serotonin 728 99.74 Very High Very High Very High
Pain 66 99.60 Very High Very High Very High
Spinal cord 16 99.32 Very High Very High Very High
Fibrositis 40 97.24 Very High Very High Very High
rheumatoid arthritis 204 96.56 Very High Very High Very High
Analgesic 24 95.48 Very High Very High Very High
antagonist 38 94.28 High High
cytokine 91 92.00 High High
Neuropeptide 40 87.84 High High
agonist 40 75.52 Quite High
Disease Link Frequency Relevance Heat
Obesity 32 99.84 Very High Very High Very High
Pain 59 99.60 Very High Very High Very High
Breast Cancer 174 99.20 Very High Very High Very High
Aids-related Complex 648 98.44 Very High Very High Very High
Sleep Disorders 40 97.24 Very High Very High Very High
Endometriosis (extended) 251 96.72 Very High Very High Very High
Rheumatoid Arthritis 204 96.56 Very High Very High Very High
Sprains And Strains 190 93.88 High High
Lifespan 24 93.68 High High
Apoptosis 50 91.12 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Beyond increasing concentrations of serotonin, E2 also modulates the actions of serotonin because the activation of E2 receptors affects the distribution and state of serotonin receptors.
Positive_regulation (activation) of E2 associated with serotonin
1) Confidence 0.27 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC1327664 Disease Relevance 0.12 Pain Relevance 0.49
Increased E2 in the presence of progesterone increases activation of 5HT2A receptors, while increased E2 in the absence of progesterone increases activation of 5HT1A receptors.
Positive_regulation (increased) of E2
2) Confidence 0.27 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC1327664 Disease Relevance 1.12 Pain Relevance 0.11
Under the prevailing theory of cumulative E2 exposure, obesity (which increases E2 levels[146]) would always be expected to increase breast cancer risk.
Positive_regulation (increases) of E2 associated with breast cancer and obesity
3) Confidence 0.27 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC1327664 Disease Relevance 1.05 Pain Relevance 0.09
Higher levels of E2 in the presence of progesterone upregulate E2 ?
Positive_regulation (upregulate) of E2
4) Confidence 0.24 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC1327664 Disease Relevance 0.11 Pain Relevance 0.49
Adding a role for serotonin does not conflict with this idea, but it does help explain several epidemiological findings that are not accounted for by a relationship between increased E2 exposure alone and breast cancer.
Positive_regulation (increased) of E2 associated with breast cancer and serotonin
5) Confidence 0.24 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC1327664 Disease Relevance 1.46 Pain Relevance 0.17
Increased E2 in the presence of progesterone increases activation of 5HT2A receptors, while increased E2 in the absence of progesterone increases activation of 5HT1A receptors.
Positive_regulation (Increased) of E2
6) Confidence 0.24 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC1327664 Disease Relevance 1.06 Pain Relevance 0.11
Mammary gland gene expression: response to E2
Positive_regulation (response) of E2 in Mammary gland
7) Confidence 0.23 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1852652 Disease Relevance 0.40 Pain Relevance 0
For each parameter, the following were calculated: a) the lowest observable effect level (LOEL) dose (the lowest dose causing a statistically significant effect); b) the peak response [the dose(s) at which the response reaches a plateau or the highest response is achieved]; c) the half-maximal dose (the amount of E2 inducing half the maximal response); and d) the fold change (the peak response divided by the response of the ovariectomized control).
Positive_regulation (inducing) of E2
8) Confidence 0.23 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1852652 Disease Relevance 0 Pain Relevance 0
The expression of Msx2 and amphiregulin mRNAs, two estrogen-regulated genes (Mallepell et al. 2006; Phippard et al. 1996), increased monotonically with increasing doses of E2 in both CD-1 and C57B16 mice (Figure 2 and Table 1).


Positive_regulation (increasing) of E2
9) Confidence 0.20 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1852652 Disease Relevance 0.34 Pain Relevance 0
E2 concentrations increase steadily during pregnancy, peaking at about 100 times normal cycling levels [3].
Positive_regulation (increase) of E2
10) Confidence 0.20 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC1327664 Disease Relevance 1.04 Pain Relevance 0.09
E2's upregulation of 5HT2A in the spinal cord could be a factor in the development of fibromyalgia, which presents as increased generalized pain sensation.
Positive_regulation (upregulation) of E2 in spinal cord associated with pain, fibrositis and spinal cord
11) Confidence 0.17 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC1327664 Disease Relevance 1.25 Pain Relevance 1.52
This contrasts the lack of response of hpg AVPV kisspeptin neurons to E2 replacement.
Positive_regulation (response) of E2 in neurons
12) Confidence 0.16 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.67 Pain Relevance 0.07
Functional studies with E2 administration (which resulted in measurable increases of circulating E2 levels and evidence of effects in the ARC) failed to increase the number of immunodetectable kisspeptin neurons, and levels were unable to be restored to those observed in WT.
Positive_regulation (increases) of E2 in neurons associated with aids-related complex
13) Confidence 0.16 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.10 Pain Relevance 0
E2 levels were significantly higher in mice receiving E2-filled capsules compared to control OVX mice receiving empty capsules, and uterine weights increased significantly in both the E2-treated OVX WT and hpg females (data not shown).
Positive_regulation (increased) of E2 in uterine
14) Confidence 0.15 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.11 Pain Relevance 0
g/mouse) or its vehicle, followed 24 h later by P4 (2 mg/mouse per day for 2 days) or its vehicle and uteri collected 24 h after the last injection; c) a single injection of E2 (1 ?
Positive_regulation (injection) of E2
15) Confidence 0.14 Published 2009 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2724541 Disease Relevance 0 Pain Relevance 0.14
E2 levels were significantly higher in mice receiving E2-filled capsules compared to control OVX mice receiving empty capsules, and uterine weights increased significantly in both the E2-treated OVX WT and hpg females (data not shown).
Positive_regulation (increased) of E2 in uterine
16) Confidence 0.13 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.17 Pain Relevance 0
E2 levels were significantly higher in mice receiving E2-filled capsules compared to control OVX mice receiving empty capsules, and uterine weights increased significantly in both the E2-treated OVX WT and hpg females (data not shown).
Positive_regulation (higher) of E2 in uterine
17) Confidence 0.13 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.17 Pain Relevance 0
However, defeminization can occur by an increased level of estradiol [6,33,34], and perhaps masculinization by affecting cyclooxygenase-2 (COX-2) regulation to increase prostaglandin E2 (PGE2) [35].
Positive_regulation (increase) of E2
18) Confidence 0.10 Published 2010 Journal BMC Genet Section Body Doc Link PMC2912782 Disease Relevance 0.09 Pain Relevance 0
E2 levels were significantly higher in mice receiving E2-filled capsules compared to control OVX mice receiving empty capsules, and uterine weights increased significantly in both the E2-treated OVX WT and hpg females (data not shown).
Positive_regulation (increased) of E2 in capsules
19) Confidence 0.05 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.11 Pain Relevance 0
Interestingly, increase in serum levels of E2 was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05).
Positive_regulation (increase) of E2 in spine
20) Confidence 0.05 Published 2003 Journal Arthritis Res Ther Section Abstract Doc Link PMC165058 Disease Relevance 0.26 Pain Relevance 0.18

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