Steroid effects mostly mediated via glucocorticoid receptor?!

[Foreverbrad]

Anyone able to debunk this? Interesting if true, and makes sense that displacing catabolic hormones (cortisol) would be very important.

Structural Requirements For An Optimal Anti-Catabolic Steroid

This post will be a bit long, but I hope it is worth it. I think @Jsaute21 and @dand will find it highly interesting but the information here applies just as much to females wishing to preserve lean tissue and prevent the catabolism that often occurs with aging. Here we go. Lately, I have been...

raypeatforum.com

 

[Foreverbrad]

Meanwhile in other studies:

Glucocorticoid antagonism by exercise and androgenic-anabolic steroids - PubMed

This work evaluated the anticatabolic capacity of androgenic-anabolic steroids and exercise (contractile activity) in inhibiting skeletal muscle atrophy associated with excessive levels of circulating glucocorticoids. With androgenic-anabolic steroids, most binding studies indicate that they...

pubmed.ncbi.nlm.nih.gov

Steroids had only weak affinity for that receptor. But maybe they only tried basic ones like Test. All this shit is behind fucking paywalls.

 

[Foreverbrad]

Template:Relative affinities of anabolic steroids and related steroids - Wikipedia

en.wikipedia.org

Tren is about 20x more affinity for GC receptor than Test but neither have particularly high affinity.

 

[Foreverbrad]

Important note: the Wikipedia table uses Dexamethasone as the reference for the GC receptor rather than Cortisol, which is 20-30x higher affinity.

This means Tren has notionally 60 to 90% of the binding affinity of naturally produced cortisol.

 

[Foreverbrad]

Next problem: binding is directly related to concentration.

Normal cortisol concentration is 140-690nmol/L
Normal testosterone concentration is 10-35nmol/L

I know for myself I got 500nmol/L cortisol and taking 500mg of test gives me 100nmol/L of test in my blood.

So it’s still gonna be majority cortisol on that receptor unless you take something like 2.5 grams of tren (would achieve 50/50 for me) and not even worth trying with test.

Inhibiting cortisol somehow at source or blocking the receptor with a less harmful (androgenic = harmful) substance would be far more efficient.

 

[Foreverbrad]

We can take Metyrapone or Ketoconazole to prevent cortisol from being created, they do have side effects.

Ketoconazole causes liver failure in 15% of long term users and also is anti-androgenic but we are taking steroids anyway so doesn’t matter.

Long-term treatment with metyrapone is usually discouraged due to the contradictory increase in ACTH production, acne, hirsutism, hyperkalemia, edema, and other mineralocorticoid effects.

Mifepristone exists to block the GC receptor but it’s brutally expensive and not in incel budgets.



I wonder what else we can take to block muscle catabolism.

The steroid Gestrinone each 2.5mg pill would be equivalent to 50mg of Tren for GR-blocking purposes but might have very unwanted side effects as it’s basically a birth control pill.