Glucocorticoid receptors

[TalkingAnt]

We know androgen receptors (AR) are of importance to sexual function. For instance, Androgen Deprivation Therapy used to treat prostate cancer in young men can cause sexual dysfunction similar in many ways to PSSD [1]. Additionally, finasteride has been shown to upregulate AR [2,3].

But what about glucocorticoid (cortisol) receptors (GR)?

GR activation can modulate AR expression, and vice versa [4,5]. GR are found in brain regions where there is also dense AR [6].

In one study, SSRI users had higher evening cortisol levels and showed decreased cortisol suppression after dexamethasone (GR agonist) ingestion [7]. This could suggest SSRI's causing problems with GR.

GR activation decreases expression of 5-HT1A [8]. This serotonin receptor is theorized to be important in PSSD pathology.

Over-activation of GR can cause the release of excess free T and DHEA [8]. My own blood tests show high DHEA and free T.

Dexamethasone is a strong GR agonist. Some PFS'ers have reported feeling better while on it.

Chronic lithium chloride injection upregulates GR in rat brains [8]. A woman here (bunny) reported she was cured from PSSD while taking lithium (among other simultaneous treatments).

Curcumin reduces effect of GR activation [8]. Some PSSD'ers report feeling better on curcumin.

Mifepristone (RU-486) is a GR antagonist. Some PFS'ers have seen positive results via short, low-dose cycles of mifepristone.

With all these links to GR, I think it is an important topic for PSSD research. Could we have caused our GR to become stuck in an upregulated or downregulated state? Is cortisol production affected as well? Do problems with GR cause problems with AR, or vice versa? Could AR and GR problems be at the root of PSSD? Or are AR/GR issues instead caused by something further down the chain of effects from PSSD?

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735098/
2. https://www.ncbi.nlm.nih.gov/pubmed/21557276
3. https://sci-hub.tw/http://www.ncbi.nlm. ... d/29675596
4. https://www.ncbi.nlm.nih.gov/pubmed/8809674
5. https://www.smartscitech.com/index.php/ ... e/view/785
6. https://www.karger.com/Article/FullText/337663
7. https://www.ncbi.nlm.nih.gov/pubmed/21458959
8. https://www.selfhacked.com/blog/glucoco ... -receptor/

[supertucker1]

I’ve raised the topic of cortisol and glucocorticoid receptors before, but it never received much attention. The following study is direct evidence of PSSD’s link to stress hormones and why most of us don’t respond to testosterone therapy.


https://www.ncbi.nlm.nih.gov/m/pubmed/1 ... e%20sexual

[Ghost]

Thanks for posting this. I'll look into it as well. I admit that I haven't really looked much at these receptors before.

[Luis Fernando Lopez]

Going on PubMed and searching "sertraline ru486" yielded these two resultss.

https://www.nature.com/articles/mp20112 ... rigin=ppub
https://www.ncbi.nlm.nih.gov/pubmed/20231081

[DrugsAreBad]

Very interesting post, TalkingAntColony. Adding to this, some people have had positive results with Inositol, which is apparently affected by Lithium and somehow related to cortisol levels.

Lithium treatment has been found to inhibit the enzyme inositol monophosphatase, involved in degrading inositol monophosphate to inositol required in PIP2 synthesis. This leads to lower levels of inositol triphosphate, created by decomposition of PIP2.[1]

Hippocampal myo-inositol was significantly related to blood cortisol.[2]

• 1. https://en.wikipedia.org/wiki/Lithium_( ... hypothesis
  2. https://www.biologicalpsychiatrycnni.or ... 0155-0/pdf

[TalkingAnt]

Also, I have two minor alleles in the NR3C1 gene, which encodes GR. The SNPs are rs7701443 and rs12521436.

I havent done a 24h cortisol test, but on a morning fasted blood test I showed low cortisol. I tend to take a while to feel fully awake in the mornings, so I suspect I have a weak cortisol awakening response.

[TalkingAnt]

Regarding lithium, this study shows it interacts with GR and HPA axis:

https://journals.plos.org/plosone/artic ... ne.0027613

[iull1k]

Interesting, why my post was deleted from here?

[Jaxx]

Interesting, why my post was deleted from here?

Was it? There are 2 simular topics active (both mentioning cortisol), perhaps you mean this post? http://www.pssdforum.com/viewtopic.php? ... 906#p21906

[iull1k]

Interesting, why my post was deleted from here?

Was it? There are 2 simular topics active (both mentioning cortisol), perhaps you mean this post? http://www.pssdforum.com/viewtopic.php? ... 906#p21906

Oh yes, sorry, my mistake.