Serotonergic 5-HT2A receptor stimulation induces steroid 5alpha-reductase gene expression in rat C6 glioma cells via transcription factor Egr-1.
"Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of depressive mood disorders and well known to inhibit the reuptake of neurotransmitter serotonin into nerve terminals. Thus, it seems conceivable that these drugs may induce the outflow of serotonin from the synapse as a consequence of inhibiting the reuptake, resulting in the stimulation of glial cells surrounding nerve terminals. On this hypothesis, the effect of serotonin on steroid 5alpha-reductase type 1 (5alpha-R) gene expression in rat C6 glioma cells was examined as one of the in vitro model experiments for investigating the indirect influence of SSRIs on glial cells. Serotonin elevated 5alpha-R mRNA and protein levels through the stimulation of serotonin 5-HT2A receptors, and also elevated Egr-1 mRNA and protein levels prior to 5alpha-R gene expression in the glioma cells. Furthermore, serotonin failed to significantly increase 5alpha-R mRNA levels in the cells preloaded with the antisense oligodeoxynucleotide targeted on Egr-1 gene. These results indicate that serotonin may stimulate 5alpha-R gene expression via transcription factor Egr-1 in glial cells, thus suggesting that serotonin flowing out of the serotonergic synapse may be implicated in SSRI-induced changes in neurosteroid metabolism in brain." https://www.ncbi.nlm.nih.gov/pubmed/15936112
Thanks for bringing this to attention. Just read a few stories last night of severe PSSD from people who used nothing but 5-HT as a supplement. You hear stories about PSSD from people who have used MDMA as well. Excess inter-synaptic serotonin appears to be the driving force behind PSSD, not the SSRIs themselves
But it is absurd, it does not inhibit 5.alpha reductase! They’re all shitty drugs!
The study you posted indicates that 5-alpha reductase type-1 mRNA is increased in glial cells (resident cells in the brain that are related to macrophages) by a pathway that is dependent upon a serotonin receptor acting through the Egr-1 transcription factor.
Egr-1 has been shown to be increased as a response to an anti-androgenic effect.
5-ar type 1 has been shown to be negatively regulated by androgens in the brain. So, it stands to reason that it is positively regulated by lack of androgen or an other anti-androgenic effect.
The anti-androgenic effect could be reduction of DHT via increasing the rate of the reductive DHT -> A-diol reaction catalyzed by 3a-HSDs or by decreasing the rate of the oxidative A-diol -> DHT “backdoor pathway of androgen production” by some 3a-HSD and RDH enzymes. These effects have been observed of SSRIs, but I’m not sure how this would occur from excess serotonin since it assumed SSRIs have this effect on enzymes at concentrations that are insignificant in blocking serotonin reuptake.
For instance, imipramine, which potently blocks serotonin reuptake, was found to have no effect in increasing allopregnanolone.
There is some explanation in this post, but it is only speculative.
Do you this could be due to the drug damaging serotonin axons?
There were no axons harmed in this study. They were a culture of glial cells in a petri dish. These are multifunctional immune cells that I think surround neurons.