So for some time now I’ve been thinking how our symptoms vary between individuals so much. While some get mostly sexual sides, other get systematic impact on several tissues.
Looking into 5 alpha reductase type 2 (5AR2) this just doesn’t sit well with me.
So for some time I’ve been researching 5 alpha reductase type 3 (5AR3). I see that it’s been mentioned a few times on here before but it’s not been researched much at all.
Many people probably know that finasteride is a very potent inhibitor of 5AR2, but not very strong inhibitor of 5AR1. But what’s interesting is it’s effect on 5AR3. Finasteride (and dutasteride) are both potent inhibitors of 5AR3 as well.
When finasteride was developed, they looked into a population of people who has 5 alpha reductase deficiency, called “Guevedoce”. These people have a mutation in the SRD5A2 gene, the gene coding for 5AR2.
They are basically “normal”, except that their genitalia and prostate is not fully developed. The gene coding for 5AR3 (SRD5A3) is still functioning in these individuals. 5AR3 is expressed in a lot of tissues around the body, while 5AR2 is more tissue specific.
5AR3 is involved in a reaction called “N-glycosylation”.
Glycosylation is critical for physiological and pathological cellular functions
The pathogenesis of many autoimmune diseases, such as immunoglobulin A (IgA) nephropathy, systemic lupus erythematosus and inflammatory bowel disease, involves abnormal glycosylation of one or more glycoproteins; diabetes involves abnormal O -linked N -acetylglucosamine-mediated signalling and enhanced glycation of multiple proteins.
There are three types of glycosylation disorders sorted by the type of alterations that are made to the glycosylation process: congenital alterations, acquired alterations and non-enzymatic acquired alterations. All these diseases are difficult to diagnose because they do not only affect one organ, they affect many of them and in different ways. As a consequence, they are also hard to treat.
I haven’t had time yet to understand this fully, and there’s very little (or none at all) research done on the effects of 5AR3 inhibition. But reading more about it, it does seem kind of likely it might be involved in the pathology of PFS.
“5AR3 expression at the mRNA level is higher than 5AR1 and 2 in frontal cortex, heart, colon, stomach, liver, pancreas, lung, BPH, prostate, testis, mammary gland, brain, cervix, ovary, dermis, epidermis, total skin, small intestine, spleen, and kidney
5AR2 mRNA was the most abundant in BPH and muscle”.