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Vit A, Aromatase, Estrogen and Copper

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Aromatase activity induction in human adipose fibroblasts by retinoic acids via retinoic acid receptor α

Abstract
Estrogen synthesis in adipose tissue is associated with the development of breast cancer. Tumors are preferentially found in breast quadrants with strongest expression of the cytochrome P450 aromatase (encoded by the gene CYP19A1). Several promoters regulated by various hormonal factors drive aromatase expression in human breast adipose fibroblasts (BAFs). As adipose tissue is a major source of retinoids, in this study, we investigated their role in the regulation of aromatase expression. The retinoids all-trans-retinoic acid (at-RA) and 9-cis-RA induce aromatase activity in human BAFs. In BAFs, at-RA induces aromatase gene expression via promoter I.4. In 3T3-L1 cells, both retinoids specifically drive luciferase reporter gene expression under the control of aromatase promoter I.4, whereas other promoters active in human adipose tissue are insensitive. Activation by retinoids depends on a 467 bp fragment (−256/+211) of promoter I.4 containing four putative retinoic acid response elements (RAREs). Site-directed mutagenesis revealed that only RARE2 (+91/+105) mediates the retinoid-dependent induction of reporter gene activity. In 3T3-L1 preadipocytes and human BAFs, RA receptor α (RARα (RARA)) expression is predominant, whereas RARβ (RARB) or RARγ (RARG) expression is low. Electrophoretic mobility shift assays with nuclear extracts obtained from human BAFs and 3T3-L1 cells identified a specific RARE2-binding complex. Retinoids enhanced complex formation, whereas pre-incubation with anti-RARα antibodies prohibited the binding of RARα to RARE2. Chromatin immunoprecipitation showed RA-dependent binding of RARα to the RARE2-containing promoter region in vivo. Furthermore, we provide evidence that RARE2 is also necessary for the basal activation of promoter I.4 in these cells. Taken together, these findings indicate a novel retinoid-dependent mechanism of aromatase activity induction in adipose tissue.

https://jme.bioscientifica.com/view/journals/jme/51/2/247.xml

Aromatase, also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens.

https://en.wikipedia.org/wiki/Aromatase

Estrogen Intake and Copper Depositions: Implications for Alzheimer's Disease?

Abstract
We present a patient with chronic postmenopausal estrogen intake with presence of Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the pathophysiological mechanisms of estrogen intake and copper accumulation in various tissues, including the central nervous system. Sonography was compatible with copper accumulation in the basal ganglia, but the patient showed no clinical signs of Wilson's disease. Magnetic resonance imaging and positron emission tomography revealed a typical pattern for Alzheimer's disease. We propose increased copper levels as a direct effect of estrogen intake due to an augmented ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free serum copper on accompanying Alzheimer's disease, knowing that copper plays a crucial role in the formation of amyloid plaques and tau aggregation. This might offer a partial explanation for the observation that postmenopausal estrogen therapy is associated with a higher risk of mild cognitive impairment and Alzheimer's disease.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105953/

lil chick and Даниил have reacted to this post.
lil chickДаниил

 

Estrogen is a problem in dairy:

Previous studies have shown that about 60–80% of estrogens come from milk and dairy products in western diets (75). Although the oral bioactivity of free 17β-estradiol and oestrone may be a bit low, but oestrogen sulphate as a main conjugate in milk, has a relatively high oral bioactivity (9). Recent epidemiological studies indicating a very strong relation between milk and dairy products high consumption and high incidence of testicular and prostate cancers (76). In the following pages of current review the estrogens and their metabolites content of human diets with especial emphasis on milk and dairy products is summarized. Moreover, the possible impact of milk and dairy products estrogens on human health along with analytical methods of estrogens quantification are discussed.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524299/

Table 2:

The concentrations (ng/ml or ng/g) of progesterone, estrogens in milk and milk products ()

Hormones Milk Cream Butter Yogurt Gouda cheese
Progesterone 9.81 48.6 141 13.3 44.2
17β-estradiol 0.02 0.03 0.3 0.02 0.03
Estreone 0.13 0.26 1.47 0.16 0.17

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524299/

rockarolla and Даниил have reacted to this post.
rockarollaДаниил

Estrogen synthesis in adipose tissue is associated with the development of breast cancer. Tumors are preferentially found in breast quadrants with strongest expression of the cytochrome P450 aromatase (encoded by the gene CYP19A1). Several promoters regulated by various hormonal factors drive aromatase expression in human breast adipose fibroblasts (BAFs). As adipose tissue is a major source of retinoids, in this study, we investigated their role in the regulation of aromatase expression. The retinoids all-trans-retinoic acid (at-RA) and 9-cis-RA induce aromatase activity in human BAFs. In BAFs, at-RA induces aromatase gene expression via promoter I.4. In 3T3-L1 cells, both retinoids specifically drive luciferase reporter gene expression under the control of aromatase promoter I.4, whereas other promoters active in human adipose tissue are insensitive. Activation by retinoids depends on a 467 bp fragment (−256/+211) of promoter I.4 containing four putative retinoic acid response elements (RAREs). Site-directed mutagenesis revealed that only RARE2 (+91/+105) mediates the retinoid-dependent induction of reporter gene activity. In 3T3-L1 preadipocytes and human BAFs, RA receptor α (RARα (RARA)) expression is predominant, whereas RARβ (RARB) or RARγ (RARG) expression is low. Electrophoretic mobility shift assays with nuclear extracts obtained from human BAFs and 3T3-L1 cells identified a specific RARE2-binding complex. Retinoids enhanced complex formation, whereas pre-incubation with anti-RARα antibodies prohibited the binding of RARα to RARE2. Chromatin immunoprecipitation showed RA-dependent binding of RARα to the RARE2-containing promoter region in vivo. Furthermore, we provide evidence that RARE2 is also necessary for the basal activation of promoter I.4 in these cells. Taken together, these findings indicate a novel retinoid-dependent mechanism of aromatase activity induction in adipose tissue.

https://jme.bioscientifica.com/view/journals/jme/51/2/247.xml

@tim-2 Yeah copper and estrogen are huge part of health issues today for man and for woman. My grandfather died from prostate cancer, my father had it also. When I look at it I think it is for sure from high estrogen, copper, low zinc... Girls they are doomed basically from the moment when they start with anticonception pills.. Estrogen goes up, they start accumulating copper and if they go even on plant based diet where they are eating nothing but nut butters, chocolate, legumes etc. with no red meat in the diet. THey will have serious health issues really quick.. My sister is basically the same case + she has two kids(so her estrogen and copper was really high for a long time) and what is even worse she has a lot of amalgams. That will not end well.. She had already two friends in their 20s who died from breast cancer crazy.. She works in hospital with CT scan and before that with X-ray so she even got good amount of radiation.. What is sad is that I can't talk about this with her. She believes only doctors and if I start talking about minerals heavy metals etc.. She would tell me that I am nuts heh..

This hair tissue mineral analysis guy has a good videos on it

https://www.youtube.com/watch?v=deusGYkl-gg

https://www.youtube.com/watch?v=vbAeu7qYfco

 Every woman should understand this..

puddleduck and tim have reacted to this post.
puddleducktim

I wonder if this helps explain the "kaflouie" effect.

Headaches and food attacks aren't always about hormones, BUT

My number of headaches and food attacks were always higher during hormonal times.

puddleduck has reacted to this post.
puddleduck

This article contradicts the negative perspective on dairy above. It shows that estrogen levels are similar in meat, eggs and dairy. Oddly boar is very high in estrogen.

I wonder if vA plays a role in children reaching puberty younger? I've seen discussion about carbohydrate rich diets causing younger puberty, I guess that could be caused by insulin increasing aromatase as well. Would it be logical to conclude that moderate carbohydrate, lower vA diets might prevent early puberty?

@jiri

Ok thanks I'll have a look.

@lil-chick

I think that if ones liver function isn't that great then hormones can be far more problematic.

Даниил has reacted to this post.
Даниил

Nicotine and caffeine inhibit aromatase while alcohol promotes it.

Даниил has reacted to this post.
Даниил

Thanks for interesting information, @tim-2

Personally, I notice estrogenic symptoms after eating a large amount of meat. For me, this manifests itself as laziness, shyness, introversion. I don't notice anything like this from beans. However, maybe there is a dump of VA? I'm not sure. I wonder if this problem concerns fish? I haven't found anything on this topic on the Internet.

tim has reacted to this post.
tim
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