Can someone explain to me how PFS leads to low Vitamin D?

General Discussion
#22

25(OH)Vitamin D3 (Calcidiol) is degraded by an enzyme called 24-hydroxylase (CYP24A1). Stolzt and others have found that CYP24A1 is under control of androgen signaling:

To summarize, our results demonstrate that androgen (DHT) signaling controls 24-hydroxylase degradation by regulating Pgr expression at the transcriptional and translational levels (Fig. 6B).

We have demonstrated that DHT [negatively] regulates the induction of 24-hydroxylase mRNA levels. (Stolzt, 2006)

androgen deficiency within renal function acts to enhance 24-hydroxylase expression and suppresses the actions of vitamin D

These findings uncover an important role for androgen in vitamin D homeostasis

These papers have clearly laid out that Vitamin D3 levels are positively driven by AR signaling through negative regulation of CYP24A1. In other words, low AR signaling will result in low Vitamin D3 levels.

It is well documented in this forum that PFS patients often present with low Vitamin D3 levels. This is one of many smoking guns which point to a deregulated AR signal in PFS patients, as do low 3a-diol-G, deregulated T, LH, FSH and estradiol, for the same reason.

If it increasingly becomes recognized that PSSD and PAS patients are presenting with similar hormonal abnormalities, this alone should be enough proof imo that we have a likely common denominator here at the AR level.

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#23

Any thinking on the fact that autoimmune patients also have low vitamin D?

#24

Autoimmune disease represents a class comprised of over 80 different disorders. Which one specifically are you referring to? I can only assume that you are talking about what @anon5006275 stated above:

I am not clear on what the basis of this statement and diagnosis is.

To answer your question, maybe you need to take a different angle. AR deregulation has been shown to play a key role in modulating immune response and auto-immune disorders:

Altogether, androgen/AR plays distinct roles in individual immune cells, and targeting androgen/AR may help in treatment and management of immune-related diseases.

So given that AR deregulation seems to be key in immune-related diseases, it would make a lot of sense that Vit D3 will also will be deregulated, given what I cited in my previous post. Imo it makes more sense that changes in immune response with PFS patients are a manifestation of AR deregulation rather than have any role at the root cause level.

https://www.sciencedirect.com/science/article/pii/S0002944012005731

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#25

@awor if it’s dependent on androgen signaling why did I have near 0 levels of vitamin D before I even took propecia and I still had an above average sex drive and no symptoms of low androgens?

#26

Maybe another survey might work here…I have used SP+ accutane never had low vitD test results…

#27

The AR mediated pathway I cited is involved in degradation, as mentioned. The other side of the story is the production and metabolism one. Enzymes such as CYP2R1 and CYP27B1 are involved there. Furthermore, skin and organs such as kidneys are also involved in the supply side of Vitamin D forms. The whole process frankly is quite complex, and I cannot tell you why you had low Vit D3 levels pre PFS. Have you ever asked a doctor? Having said this, Vitamin D deficiency is quite common, due to lifestyle (i.e. lack of sun exposure) and for other reasons. As I said, Vit D3 deregulation is just one of many smoking guns, there are many more:

#28

Source please! Thanks.

#29

In addition to what’s been written: Recently we published a document which included a detailed and fully cited outline of how overexpression of the AR mechanistically recapitulates the effects of polyglutamine expanded AR, which underlies the broad symptoms of SBMA.

In SBMA, serum low vitamin D is also a very frequent finding ​(Querin et al., 2015)​. During our work, the staff collated all existing PFS patient reports of serum vitamin D levels. The reported values in our cohort are often also low. Given this is an observed effect in a disease state recapitulated by WT-AR amplification, this would support that vitamin D levels would frequently be low in PFS.

It is of note that other frequently reported serum findings in SBMA, including elevated metabolic markers (total cholesterol, triglycerides, fasting glucose and insulin etc) and creatine kinase are also well reported in PFS patient anecdotes. Like in SBMA, these are heterogeneous and not frequent to the extent of a determinable biomarker.