DHT Reduces Glucocorticoid Effects

haidut

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I mentioned this on one of the Danny Roddy shows, but wanted to post this study here as many people have been asking me for references over email. In addition to reducing glucocorticoid effects, DHT is also an estrogen "receptor" antagonist as I posted in another thread.
DHT Is Estrogen "receptor" Antagonist


This study found that DHT reduced expression of GR, which reduces the effects glucocorticoids can exert on tissues where the GR is expressed. It is worth noting that DHT also increases cortisol degradation through 11b-HSD2 and excretion by the liver, as I mentioned on one of the Danny Roddy shows.
Androgens modulate glucocorticoid receptor mRNA, but not mineralocorticoid receptor mRNA levels, in the rat hippocampus. - PubMed - NCBI

"...Four days prior to sacrifice, these animals were either adrenalectomized or sham operated. GR, MR and AR mRNA were measured in the hippocampal subfields using in situ hybridization. In the CA1 region, dihydrotestosterone treatment of castrates decreased GR mRNA levels to 69 percent of levels found in gonadally intact rats and prevented the adrenalectomy-induced increases in GR mRNA observed in the gonadally intact and castrated animals. No changes in GR mRNA were observed in the CA3 region or dentate gyrus, where AR expression is low or absent."
 
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Blue Jefe

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@haidut I just want to point out that upregulating the GR in the brain has shown in several studies to have a positive effect on depression/anxiety/steroid resistance. The GR is a complicated beast that I haven’t fully figured out yet.

Leonurine promotes neurite outgrowth and neurotrophic activity by modulating the GR/SGK1 signaling pathway in cultured PC12 cells. - PubMed - NCBI

An example here where GR upregulation led to increased Neurotrophins and neurite outgrowth and the effect was abrogated by RU486. There is some evidence that in ME/CFS, a disease I meet the diagnostic criteria for, the GR may be hyperresponsive or underresponsive depending on the study.

https://www.hindawi.com/journals/mi/2018/3972104/

Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
 
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