Looking for aromatase deficiency in the raw datas

[trollo]

Hello everybody. I recently discovered that i have a severe deficiency of estradiol and as i did 23andMe test 10 years ago i d need to find a company that can look inside the raw datas to look for aromatase deficiency SNPs as i'm not able to do it myself. Does anybody here knows who can i ask for about that?

 

[datadragon]

We show that male and female hormones differentially regulate the expression of a novel autism candidate gene, retinoic acid-related orphan receptor-alpha (RORA) in a neuronal cell line, SH-SY5Y. In addition, we demonstrate that the gene RORA transcriptionally regulates aromatase, an enzyme that converts testosterone to estrogen. We further show that aromatase protein is significantly reduced in the frontal cortex of autistic subjects relative to sex- and age-matched controls, and is strongly correlated with RORA protein levels in the brain. The level of RORA expression can be regulated by both male and female hormones through their respective receptors, and that one of its transcriptional targets is CYP19A1 (aromatase), an Cytochrome CYP450 enzyme responsible for the conversion of testosterone to estrogen https://autismodiario.org/wp-content/uploads/2011/02/journal.pone_.0017116.pdf

There were also significant increases in the mRNA levels of CD38 and RORA after vitamin A supplementation. Significant differences were also observed in the gut bacteria after vitamin A supplementation. https://medicalnewsbulletin.com/vitamin-supplements-autism-symptoms-children/ Note that zinc plays a role in Vitamin A metabolism and vice versa as I've covered before in other threads I believe.

A subset of cytochrome P450 enzymes play important roles in the synthesis of steroid hormones (steroidogenesis) by the adrenals, gonads, and peripheral tissue. Cyp450 aromatase (CYP19A1) is the enzyme responsible for the irreversible androgen to estrogen conversion and crucial for sex steroid hormone synthesis. (The enzyme aromatase is responsible for the synthesis of estrogen).

The expression of both CD38 and RORA (retinoic acid receptor-related orphan receptor alpha) genes is reduced in autism spectrum disorders. Plasma retinoic acid levels increased significantly after vitamin A supplementation. The nuclear receptor RORα exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes. Astrocytes and one of their products, IL-6, not only support neurons but also mediate inflammation in the brain. Retinoid-related orphan receptor-α (RORα) transcription factor has related roles, being neuro-protective and, in peripheral tissues, anti-inflammatory. We examined the relation of RORα to astrocytes and IL-6 using normal and RORα loss-of-function mutant mice. We have shown RORα expression in astrocytes and its up-regulation by pro-inflammatory cytokines. We have also demonstrated that RORα directly trans-activates the Il-6 gene. We suggest that this direct control is necessary to maintain IL-6 basal level in the brain and may be a link between the neuro-supportive roles of RORα, IL-6, and astrocytes. Furthermore, after inflammatory stimulation, the absence of RORα results in excessive IL-6 up-regulation, indicating that RORα exerts an indirect repression probably via the inhibition of the NF-κB signaling. Thus, our findings indicate that RORα is a pluripotent molecular player in constitutive and adaptive astrocyte physiology." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795519/pdf/zpq21365.pdf

 

[trollo]

We show that male and female hormones differentially regulate the expression of a novel autism candidate gene, retinoic acid-related orphan receptor-alpha (RORA) in a neuronal cell line, SH-SY5Y. In addition, we demonstrate that the gene RORA transcriptionally regulates aromatase, an enzyme that converts testosterone to estrogen. We further show that aromatase protein is significantly reduced in the frontal cortex of autistic subjects relative to sex- and age-matched controls, and is strongly correlated with RORA protein levels in the brain. The level of RORA expression can be regulated by both male and female hormones through their respective receptors, and that one of its transcriptional targets is CYP19A1 (aromatase), an Cytochrome CYP450 enzyme responsible for the conversion of testosterone to estrogen https://autismodiario.org/wp-content/uploads/2011/02/journal.pone_.0017116.pdf

There were also significant increases in the mRNA levels of CD38 and RORA after vitamin A supplementation. Significant differences were also observed in the gut bacteria after vitamin A supplementation. https://medicalnewsbulletin.com/vitamin-supplements-autism-symptoms-children/ Note that zinc plays a role in Vitamin A metabolism and vice versa as I've covered before in other threads I believe.

A subset of cytochrome P450 enzymes play important roles in the synthesis of steroid hormones (steroidogenesis) by the adrenals, gonads, and peripheral tissue. Cyp450 aromatase (CYP19A1) is the enzyme responsible for the irreversible androgen to estrogen conversion and crucial for sex steroid hormone synthesis. (The enzyme aromatase is responsible for the synthesis of estrogen).

The expression of both CD38 and RORA (retinoic acid receptor-related orphan receptor alpha) genes is reduced in autism spectrum disorders. Plasma retinoic acid levels increased significantly after vitamin A supplementation. The nuclear receptor RORα exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes. Astrocytes and one of their products, IL-6, not only support neurons but also mediate inflammation in the brain. Retinoid-related orphan receptor-α (RORα) transcription factor has related roles, being neuro-protective and, in peripheral tissues, anti-inflammatory. We examined the relation of RORα to astrocytes and IL-6 using normal and RORα loss-of-function mutant mice. We have shown RORα expression in astrocytes and its up-regulation by pro-inflammatory cytokines. We have also demonstrated that RORα directly trans-activates the Il-6 gene. We suggest that this direct control is necessary to maintain IL-6 basal level in the brain and may be a link between the neuro-supportive roles of RORα, IL-6, and astrocytes. Furthermore, after inflammatory stimulation, the absence of RORα results in excessive IL-6 up-regulation, indicating that RORα exerts an indirect repression probably via the inhibition of the NF-κB signaling. Thus, our findings indicate that RORα is a pluripotent molecular player in constitutive and adaptive astrocyte physiology." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795519/pdf/zpq21365.pdf

Hi, i don't understand why you did that cut/paste job without any explanation and how this would responde to my question. I already know that the gene for congenital aromatase deficiency is CYP19A1 and i know 23andMe tested it but i don't know how to read the results.

 

[datadragon]

Hi, i don't understand why you did that cut/paste job without any explanation and how this would responde to my question. I already know that the gene for congenital aromatase deficiency is CYP19A1 and i know 23andMe tested it but i don't know how to read the results.

The problem is usually related more to being in an inflammatory state as this decreases cytochrome p450 enzyme activity such as I was mentioning here https://forums.phoenixrising.me/thr...mage-from-some-medications.91177/post-2448621 , as well as lowers zinc and Vitamin A levels which would cause aromatase deficiency. You are welcome to also check genetics for mutations but that is probably 95% not the issue but as you say its possible is why I posted that in reply. There are also external exposures that can lower the enzyme activity further.

 

[trollo]

The problem is usually related more to being in an inflammatory state as this decreases cytochrome p450 enzyme activity such as I was mentioning here https://forums.phoenixrising.me/thr...mage-from-some-medications.91177/post-2448621 , as well as lowers zinc and Vitamin A levels which would cause aromatase deficiency. You are welcome to also check genetics for mutations but that is probably 95% not the issue but as you say its possible is why I posted that in reply. There are also external exposures that can lower the enzyme activity further.

I've read your link. It's an odd coincidence but i'm strongly persuaded that it was Fluoxetine that in 2006 caused my estradiol deficiency because i had all symptoms of estradiol deficiency: it all began with lethargy and cronic fatigue and ginecomastia (wich passed after 2 weeks) and then years later prostate issues, infertility, occasional akathisia/restless legs syndrome, insomnia, joints issues and inflammation, tendons inflammation. I know many of these symptoms are caused by estradiol deficiency , mainly insomnia, because last winter i used a finasteride gel for alopecia thinking i wouldn t have had side effects but unexpectedly i had evident side effects wich were same than that of fluoxetine in 2006, in the blood tests i did while assuming the gel Estradiol was high and free testosterone very low (estradiol went from undetectable to near upper limit because of finasteride). After i stopped finasteride gel in July my estradiol remained high and during the following monthes i discovered that my insomnia issues were better. Now, after 6 monthes i think joints condition also seems better. So basically assuming the finasteride gel i unintentionally corrected the estradiol deficiency improving some of its effects (but my T remained low).
I think that fluoxetine made in 2006 somehow rise my estradiol to alarming levels and this would explain my severe ginecomastia issues (that i had while on fluoxetine in 2006) and that my body reacted downregulating aromatase activity and upregulating the activity of the enzyme that produces SHBG (i had high shbg, undetectable estradiol and low free T until i used finasteride gel last winter) , when i stopped fluoxetine unluckily the modifications didn't reverse back to normality and i developed an induced estradiol deficiency. Maybe the action through which fluoxetine caused my estradiol deficiency was somehow mediated by effect on Cyp450. The point is that i had to travel to my city to Rome to find a Dr who was informed about the importance of proper estradiol levels in male's health (all Drs i saw in my city said that estradiol is important only for women), it will be impossible to find a Dr who knows about the stuff you spoke about.
But i still wonder if i could have some sort of genetic predisposition to estradiol deficiency that was triggered or worsened by fluoxetine use. As i already said i've already made 23andMe test and the results are there, i only need to know how to read them.

P.S. I've already been to a Bill Walsh's trained physician and he made tests to see if i was over or under methylated, and that was not my issue.

 

[trollo]

So, is there really nobody here who knows where i can get my raw datas explained? I know for sure there are some companies like Genetic genie that do that for money, i've read it in this forum years ago somewhere.