20 replies to this topic

[kurdishfella]

 > > > > has anyone seen this study ? its from 1998 . I think they are suggesting there could be CRF1 mutations but unrelated to cushings disease>

> > > > 
> > > > I quote from the study ...No mutations affecting the CRF1-R protein have been found in all tumors analyzed. However, we found a significant overexpression of the CRF1-R messenger RNA in ACTH-secreting pituitary adenomas vs. inactive adenomas and normal pituitaries. We conclude that mutations of the CRF1-R are unlikely to be involved in Cushing's disease. We suggest that the overexpression of the CRF1-R messenger RNA may be related to a disturbed receptor regulation in ACTH-secreting pituitary adenomas...
> > > > 
> > > > https://www.ncbi.nlm.../pubmed/9745449
> > > > 
> > > > English is my 3rd language so maybe someone can explain this that understands it better 
> > > 
> > > I found 2 possible mutations that I have related to ACTH>
> > > 
> > > PDE8B https://www.selfdeco...dvanced-summary
> > > 
> > > ACE (Angiotensin I converting enzyme) https://www.selfdecode.com/gene/ace/
> > 
> > --------------
> > One mutation in human PDE8B (His350Pro), from a patient with severe adrenal hyperplasia, impaired PDE8B catalytic activity, and its expression in Hela cells resulted in increased cAMP-signaling, suggesting a role for cAMP in development of adrenal hyprerplasia. Such PDE8B mutations may not directly cause adrenal hyperplasia, however, since PDE8B KO mice do not develop adrenal tumors (Tsai and Beavo 2011). Inactivating PDE11A gene mutations are also associated with the development of adrenal hyperplasia and Cushing syndrome (Libe et al. 2008), and with Carney complex (CNC). CNC is caused by germline mutations in the alpha regulatory subunit of PKA (PRKARIA) and is associated with endocrine tumors, including nodular adrenal hyperplasia and adrenal and testicular tumors (Levy et al. 2011;Libe et al. 2011). PDE11A mutations may also play a role in susceptibility to prostate cancer (Faucz et al. 2011) and testicular germ cell tumors (TGCT) (Horvath et al. 2009).
> > ------------
> > 
> > https://www.ncbi.nlm...les/PMC4275405/
> > 
> > 
> > https://en.wikipedia...nal_hyperplasia
> > 
> 
> https://en.wikipedia...iki/Angiotensin (Angiotensin I converting enzyme)

I dont know what to think this is all so confusing. So I have mutations in my CRF1 gene specifically with the PDE8B causing excessive cortisol and the Secretion of CRH, ACTH, and cortisol is increased by stimulation of angiotensin AT(1) receptors.

So it all goes in a loop and just further pushes each other to the max?

 

here are the 2 CRF1 mutations btw I have
https://www.selfdeco...gene/crhr1-it1/
https://www.selfdeco...mgc57346-crhr1/

 

 

So its obvious that there is something wrong with my genetics specificaly the cortisol/fight or flight stress related ones, which is why I think I have such bad anxiety . Can anyone help me out so I can understand this simple? 

Edited by farshad, 19 March 2018 - 07:45 PM.

[kurdishfella]

Here are some other cortisol genes I found I have problems with(does this make sense to anyone?): 

 

https://www.selfdeco...dvanced-summary -  Constitutive activation of the adenylate cyclase enzyme leads to over-production of several hormones IE cortisol?

 

https://www.selfdeco...dvanced-summary -  Mutations in the NR3C2 gene lead to a nonfunctional or abnormally functioning mineralocorticoid receptor protein that cannot properly regulate the specialized proteins that transport sodium and potassium

 

 

2 others

 

https://www.selfdeco...anced-summary  

 

https://www.selfdeco...dvanced-summary

 

 

Do you guys think all of this can be fixed just by taking Metyrapone? Since it blocks cortisol.

Edited by farshad, 19 March 2018 - 08:30 PM.

[kurdishfella]

How am I supposed to decipher all this?..

 

https://www.selfdeco...m/gene/cyp17a1/ - this condition affects the function of certain hormone-producing glands

 

https://www.selfdeco.../gene/ppargc1b/ -  Activates transcritional activity of estrogen receptor alpha, nuclear respiratory factor 1 (NRF1) and glucocorticoid receptor in the presence of glucocorticoids. 

 

https://www.selfdeco...m/gene/txnrd2/ 

 

https://www.selfdeco...dvanced-summary -  adrenocorticotropic 

 

 

 

I Imagine the best choice would be Antalarmin (CRF1 antagonist)  but since its nowhere to be found my next best choice is Metyrapone (get from doc).

I ordered some Astressin-B  its an CRH antagonist but its topical so I dont know if it will work.

Edited by farshad, 19 March 2018 - 09:50 PM.

[kurdishfella]

im thinking I have some Unknown autoimmune disorder..*there are over 80 different types of autoimmune disorders that affect various organs, glands, systems and functions throughout the body*

Edited by farshad, 20 March 2018 - 10:57 AM.

[kurdishfella]

So reducing Cortisol will reduce ACTH and anything related to cortisol/stress right?

[kurdishfella]

can anyone based on the links and info I have provided  tell me what my issue may be? here all the cortisol mutations I got:

 

https://www.selfdeco...dvanced-summary

https://www.selfdecode.com/gene/ace/

https://www.selfdeco...gene/crhr1-it1/

https://www.selfdeco...mgc57346-crhr1/

https://www.selfdeco...dvanced-summary

https://www.selfdeco...m/gene/cyp17a1/

https://www.selfdeco.../gene/ppargc1b/

https://www.selfdeco...dvanced-summary

Edited by farshad, 22 March 2018 - 08:28 AM.

[kurdishfella]

hmm found an intresting study about ACE - https://www.ncbi.nlm...ubmed/20011602/
"CONCLUSIONS/SIGNIFICANCE: We have identified a novel Trp1197Stop mutation that results in dramatic elevation of serum ACE. "



The link between angiotensin II-mediated anxiety and mood disorders with NADPH oxidase-induced oxidative stress (ace converts to ace 2)

https://www.ncbi.nlm...les/PMC3312460/




ACTH -
https://www.ncbi.nlm...les/PMC1884405/



also whats the difference between ACE And ACTH? Are they connected?

Edited by farshad, 22 March 2018 - 07:33 PM.

[kurdishfella]

I think im in a  hyper-oxidative state.

[kurdishfella]

abnormally high levels of CRH have been found in the cerebrospinal fluid of people that have committed suicide.^[10]

 

This is also where I feel this constant pressure. pic/gif of the Cerebrospinal fluid (CSF) ... 

 

So this must be the CRF1 mutations I have which causes high lvls of ACTH and this pressure I have, Its extachly at that spot too only there.

 

= hyper-oxidative stress state

Edited by farshad, 23 March 2018 - 07:04 PM.

[kurdishfella]

hmm this doesent make much sense to me.



So if cortisol inhibits CRF1(cortisol releasing hormone) that means more stress would decrease cortisol release long term? Since stress increases cortisol. But how does this apply to my problem? If I had too many CRF1 receptors/activation Also known as CRHR1 what would happen in my case? Woldnt it just keep pushing and pushing activating the ACTH and that would create more cortisol. So maybe now my CRF1 is downregulated but my cortisol is so high in my body that is needed to inhibit all the crf1 receptor activation I have. So I constantly Have high cortisol lvls in my body to inhibit CRF1? thats why im always in a anxious state. and with higher cortisol constant im learning more fear based behaviors.

Edited by farshad, 24 March 2018 - 03:36 AM.

[Caravaggio]

Could you please upload your 23andme results to NutraHacker (maybe not the most professional site but gives a good overview of the SNPs) and share the results?

 

Free version doesn't cover all SNPs so you should do the full coverage.

[kurdishfella]

Could you please upload your 23andme results to NutraHacker (maybe not the most professional site but gives a good overview of the SNPs) and share the results?

 

Free version doesn't cover all SNPs so you should do the full coverage.

https://s3-us-west-2...bc83e13cd92.pdf

 

thats free

 

should I buy a sample report? which one should I buy? the  Carrier Status report? or Complete Mutation Report?

Edited by farshad, 15 April 2018 - 10:52 PM.

[kurdishfella]

the red ones are the ones I should be worried about?

If you look at the COMT I have on both of my COMT genes the slowest possible Genotypes .  the NAT2 and GSTP1 gene  also -so all these together = very slow detoxification ? =anxiety + tumor?

 

Edited by farshad, 15 April 2018 - 11:36 PM.

[Caravaggio]

the red ones are the ones I should be worried about?

If you look at the COMT I have on both of my COMT genes the slowest possible Genotypes .  the NAT2 and GSTP1 gene  also -so all these together = very slow detoxification ? =anxiety + tumor?

 

Yes, the Catechol-O-methyltransferase (COMT) is responsible for the breakdown of epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. 

 

Too much norepinephrine causes nervousness and anxiety.

 

The Complete Mutation Report is what you want.

 

I also have 4 COMT mutations.

[kurdishfella]

Yes, the Catechol-O-methyltransferase (COMT) is responsible for the breakdown of epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. 

 

Too much norepinephrine causes nervousness and anxiety.

 

The Complete Mutation Report is what you want.

 

I also have 4 COMT mutations.

what does the complete report show?

 

COMT helps break down estrogen byproducts that have the potential to cause DNA mutations and cause cancer and tumors. (R) 

 

Im thinking maybe my body is not  detoxifying enough due to my multiple gene mutations.

 

im not sure what NAT2 and GSTP1  does.

Edited by farshad, 16 April 2018 - 04:21 PM.

[Caravaggio]

The complete report shows 45 mutations out of the 195 polymorphisms assessed compared to 16 out of 58 assessed in the free version.

 

I have 5 NAT2 mutations but they're all heterozygous, so the enzymes just work slower.

 

NAT2 handles arylamine and hydrazine drugs and carcinogens. So you would react more to hydrazine drugs and are more prone to cancer with your homozygous mutations.

 

GSTs are enzymes that use Glutathione (GSH) to detoxify xenobiotics.

 

To help detoxify xenoestrogens I'd suggest you take Indole-3-carbinol and Calcium D-Glucarate.

Edited by Caravaggio, 16 April 2018 - 06:49 PM.

[kurdishfella]

The complete report shows 45 mutations out of the 195 polymorphisms assessed compared to 16 out of 58 assessed in the free version.

 

I have 5 NAT2 mutations but they're all heterozygous, so the enzymes just work slower.

 

NAT2 handles arylamine and hydrazine drugs and carcinogens. So you would react more to hydrazine drugs and are more prone to cancer with your homozygous mutations.

 

GSTs are enzymes that use Glutathione (GSH) to detoxify xenobiotics.

 

To help detoxify xenoestrogens I'd suggest you take Indole-3-carbinol and Calcium D-Glucarate.

so based of the mutations I have I should take these 2 supplements? will they make a big difference? I never heard of them before but is there like anywhere I can read more about  my situation and maybe theres more supplements that can help me?

[kurdishfella]

so based of the mutations I have I should take these 2 supplements? will they make a big difference? I never heard of them before but is there like anywhere I can read more about  my situation and maybe theres more supplements that can help me?

 I bought the complete ... heres the full https://s3-us-west-2...5775fc3bfa3.pdf

are my mutations common? what should I take? 

So what I want is supplements that detoxify my body becuase im producing too much cells? 

Edited by farshad, 16 April 2018 - 07:55 PM.

[Caravaggio]

Here are my results just to compare: https://s3-us-west-2...b871632a0c2.pdf

 

Your NR3C1 mutation is found in patients with major depression:

 

Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response

M-L Wong, C Dong, J Maestre-Mesa & J Licinio

Molecular Psychiatry volume 13, pages 800–812 (2008)

https://www.nature.c...ticles/mp200859

 

The VKORC1 mutation makes you susceptible to bleeding while taking Warfarin because you have lower Vitamin K, do you supplement it?

 

For the SOD mutations you could try a SOD supplement.

 

Was your blood sugar measured? Should be high due to the G6PC2 mutation -> not too much carbs in diet + chromium.

 

Probably high blood lipids due to low adiponectin (ADIPOQ).

 

The PEMT mutation would even worsen this as you miss choline to act as a carrier for the fatty acids.

 

[kurdishfella]

Here are my results just to compare: https://s3-us-west-2...b871632a0c2.pdf

 

Your NR3C1 mutation is found in patients with major depression:

 

https://www.nature.c...ticles/mp200859

 

The VKORC1 mutation makes you susceptible to bleeding while taking Warfarin because you have lower Vitamin K, do you supplement it?

 

For the SOD mutations you could try a SOD supplement.

 

Was your blood sugar measured? Should be high due to the G6PC2 mutation -> not too much carbs in diet + chromium.

 

Probably high blood lipids due to low adiponectin (ADIPOQ).

 

The PEMT mutation would even worsen this as you miss choline to act as a carrier for the fatty acids.

I dont have depression just constant 24/7 fight/flight alert anxiety. 

 

No I dont supplement anything at the moment, but I dont take warfarin either.

I think my blood sugar was normal when I tested it.

the PEMT mutation worsen what? the high blood lipids? I really dont feel like I have Any problems besides this constant 24/7 anxiety and I thought first my brain released constant Cortisol and I had no tumor, but then people told me that cant happen becuase your body is made in such a way it would stop excess cortisol , So I searched for CRH releasing tumor and I find some cases very few but the CRH tumor is usually outside of the brain (dont know if that makes a difference) but I have yet to see a  case for a CRH releasing tumor in the brain which I think I have.

 

No sure what SOD is. do sod supplemens even work? SOD is SUPEROXIDE DISMUTASE? I read they dont work becuase its destroyed in the body fast, and Sod supplements are fake?

 

I think I have to find ways to detoxify my body becuase my tumor surpressing genes are out of wack, so the tumor goes away. Do you know any  other good detoxify supplements besides the 2 you mentioned ?

Made a thread https://www.longecit...oxify-the-body/

 

Edited by farshad, 16 April 2018 - 10:29 PM.

[Caravaggio]

Found an interesting text on MTHFR Support:

 

There is a reason that women are more prone to anxiety (high dopamine) and men are always looking for dangerous things to do (low dopamine). It is fascinating how the hormone estrogen can SLOW DOWN the COMT pathway, while testosterone SPEEDS UP the COMT pathway. In my opinion, this is likely why men are prone to being grumpy (low dopamine) and women are prone to excessive worry (high dopamine).

 

"The COMT enzyme activity is reduced epigenetically by estrogen

with 30% decrease in activity in females compared to males." - Sleep Med Rev. 2015 Aug;22:47-53. PMID: 25466290

 

"We report that androgens (T and DHT) increase TH protein and increase COMT, MAOA and MAOB mRNAs in the adolescent male rat substantia nigra" - BMC Neurosci. 2012 Aug 6;13:95. PMID: 22867132

 

The body truly is incredible! Balancing hormones is one of the most important things you can do to balance your genetic pathways.

 

Yours in Health,

 

Dr. Rostenberg

 

In our case it's COMT that causes high dopamine due to the delayed breakdown of dopamine. That would explain my high urine homovanillic acid (9,66 mg/g creatinine, reference range: 2,2 - 8,3 mg/g creatinine), a metabolite of dopamine breakdown.

 

My low testosterone and high dopamine could explain my anhedonia (447 ng/dL when it should be above 600 ng/dL at my age).

 

I have the level of an 80 year old :D

 

 Normal-Testosterone-Levels-By-Age.png   80.82KB   0 downloads

A. Vermeulen (1996) - although I couldn't find the study where this image comes from but the site I got it from even quoted the author's name wrong.

 

But here's a legit source with basically the same ranges for T (just in nmol/L)

 

 serume_hormone_levels.png   211.33KB   0 downloads

Journal of Clinical Endocrinology and Metabolism

Copyright 1996 by The Endocrine Society

Influence of Some Biological Indexes on Sex Hormone-Binding Globulin and Androgen Levels in Aging or Obese Males*

A. VERMEULEN, J. M. KAUFMAN, AND V. A. GIAGULLI 

Department of Endocrinology and Metabolism, Medical Clinic, University Hospital, 9000 B 

Ghent, Belgium

 

So if dopamine and testosterone have a bidirectional relationship the high dopamine could explain low testosterone.