found a great IN-DEPTH blog of which Ive copied a part (with diagrams) that suggested as such. that pdg2 among-st other inducers stimulates calcification. but there's (as i've always said) far more to it than that; the blog is long, so i've copied the tastiest part.
he also argues regarding fibrosis which is a separate issue, is just as negative.. .... see no2 but go to the site as there is a lot more...
no 1 is the following https://www.sciencedirect.com/science/article/pii/0006291X89922389
Prostaglandin D2 stimulates calcification of human osteoblastic cells
Abstract
Studies on prostaglandin (PG) regulation of bone formation and resorption metabolism have been complicated by the heterogeneity of the tissue, which involves the interaction between and the activities of two bone cell types, osteoblasts and osteoclasts. In a simplified assay system using a cultured human osteoblastic cell line which has the capacity to form calcified tissue, we determined the effects of PGs on calcification. Of the PGs tested, PGD2 has a remarkable stimulatory activity on osteoblast calcification, but that the effective form is probably a metabolite, Δ12-PGJ2. This calcification function is not cAMP-mediated. PGD2 acts directly on osteoblast to cause stimulation of calcification.
----------------------------------------------------------------
no 2
https://perfecthairhealth.com/the-ultimate-hair-loss-flowchart-why-we-lose-our-hair/
What Is Calcification?
According to medical experts, calcification is “when calcium builds up in places where it doesn’t usually appear, like the coronary arteries or brain.”
Since elderly people often have more calcification, researchers once thought this process was a part of normal aging. But it turns out the relationship between age and calcification doesn’t really exist. Calcification doesn’t have to increase with age. It can be rampant in young adults and nearly absent in older ones.
And finally, it’s also important to note that calcification is not necessarily caused by a calcium-rich diet.
So back to our flowchart. Does calcification cause fibrosis?
Probably not. Most research suggests that calcification and fibrosis can occur in the same areas, but are likely independent of each other. And while some scleroderma patients also suffer from soft tissue calcification, others just suffer from an overproduction of collagen. So calcification does not have to happen before fibrosis and vice-versa.
Knowing this, we’re ready to add calcification into our flowchart. For simplicity’s sake, we’ll remove the visuals describing a balding scalp – the “thicker, tighter, shinier skin.”
Now let’s start tracing this chart backwards. We’ve gone as far as calcification and fibrosis. So what triggers both?
Calcification And Fibrosis Precede Hair Loss…
…But What Causes Calcification And Fibrosis?
We can get an idea of what might be causing these conditions if we look at the people most likely to develop arterial calcification and fibrosis: men.
Men are almost twice as likely as women to develop calcified arterial lesions. Why is that? Researchers have long suspected that androgens might be to blame. Read: testosterone and DHT – or dihydrotestosterone.
Why is this so interesting?
Well, most doctors agree that DHT causes hair loss… But none actually know how DHT causes hair loss. If DHT triggers calcification and fibrosis, this explains how DHT causes hair loss. But to confirm this, we need to know if androgens (like DHT) actually precede arterial calcification and fibrosis.
The DHT-Calcification-Fibrosis Connection
Does DHT Cause Calcification And Fibrosis?
Research here is mixed.
On the one hand, men and women who take androgens (steroids) significantly increase their risk of arterial calcification. And in mice, DHT and testosterone injections increase arterial calcification lesions by 200-400%. The more DHT or testosterone injected, the greater the calcification. That’s a pretty strong case that androgens cause calcification.
But paradoxically, in studies done in test tubes (outside of our bodies), increased androgens don’t cause calcification. In these tests, androgens protect against calcification.
This suggests two things:
What does this suggest?
In the scalp, increased DHT plus these “mystery variables” precede both calcification and fibrosis. Knowing this, here’s our new flowchart:
So what could these mystery variables be?
Well, there are two. The first is an increase in androgen receptors. The second is an imbalance of calcification regulators. And explaining both are a bit of a mouthful. So bear with me.
A Crash Course On DHT, Androgen Receptors, And Calcification Regulators
We know that androgens alone don’t cause calcification, and that in the body, androgens must be interacting with other variables to cause calcification and fibrosis. So, what are those variables?
It appears there are two. And in 2016, researchers finally confirmed the first one: androgen receptors.
What Is An Androgen Receptor?
An androgen receptor (AR) is the place inside a cell where androgens – like testosterone and DHT – attach themselves. Think of an androgen receptor (AR) like the landing pad for DHT. Without its landing pad, DHT doesn’t bind to the cell.
Here’s a visual. This is a cell, and the yellow puzzle pieces (labeled AR) are androgen receptors:
(source)
Androgen receptors aren’t always active. They typically turn on in the presence of DHT or testosterone, then turn off when these hormones aren’t around.
The Connection Between Increased DHT And Increased Androgen Receptors
In our scalp tissues, increased androgens turn on more androgen receptors, and together, the increased DHT plus the increased androgen receptors results in calcification. Both DHT and androgen receptors must increase (not just one) for calcification to occur.
Interestingly, DHT plus androgen receptors also increase fibrosis in heart cells.
In other words, increased DHT + increased androgen receptors precede both calcification and fibrosis.
But here’s where things get tricky… Increased androgen receptors aren’t the only other variable. We know this because of DHT’s biggest paradox:
Increased tissue DHT encourages hair loss in the scalp, but encourages hair growth in the face and body.
That means that in our hairy facial and body tissues, calcification and fibrosis don’t occur. Why? Because in our bodies and face, increased DHT instead encourages hair growth – just the opposite of our scalps.
If our flowchart is accurate, this means that in the body and face, when DHT increases, androgen receptors must not increase. Otherwise, our body and facial tissues would also calcify, and hair wouldn’t grow.
But as it turns out, both balding scalps and hair-bearing body and facial tissues have increased DHT and increased androgen receptors… Yet hairy body and facial parts aren’t calcified or filled with fibrosis.
What does all of this mean?
In addition to DHT and androgen receptors, another factor must also be causing calcification and fibrosis. Either something is protecting our body and face from fibrosis and calcification, or something is causing both to happen in our scalps.
Taking this into account, here’s our new flowchart:
So, what is this new mystery variable? There are several contenders, but diving into all of them would turn this already-monstrous post into a full-blown book.
The reality is, we don’t yet know for sure.
The reason why: 99% of researchers still abide to the DHT-sensitivity argument. They say that “genetics” makes our hair follicles more sensitive to DHT, and that for unknown reasons, DHT accumulates in the scalp and eventually causes hair loss. To my knowledge, there are no current studies even exploring scalp DHT’s connection to calcification (even though when we look at broader research, the connection seems obvious).
On top of that, researchers only recently confirmed (in 2016!) that both an increase in androgens and androgen receptors are needed to cause calcification, not just one. This discovery came from cardiovascular researchers and not hair loss researchers. These fields don’t really talk to each other. Neither is very aware of the other’s work. As a result, our third mystery variable remains a mystery.
But even still, we can make a very strong case for what this variable could be.
Uncovering The New Mystery Variable
Here’s what we know: if we inject regular mice with DHT, they develop calcification. But if we inject DHT into mice who can’t produce androgen receptors, no calcification occurs. Why?
Let’s start by looking at the “engineered” mice who can’t express androgen receptors. When they receive DHT, their bodies respond by…
So how do the regular mice – the ones with androgen receptors – respond to a DHT injection? Just the opposite. When these mice receive DHT, their bodies…
This is important. Surrounding our bodies and facial hair, we don’t develop the same calcification or fibrosis that we see in balding regions of the scalp. The same isn’t true for our scalp hair. This suggests one thing:
Our new mystery variable is likely, among other things, an imbalance of calcification regulators.
What Are Calcification Regulators?
Calcification regulators are a set of (mostly) proteins with many names and functions. They regulate whether your tissues accumulate or release calcium. We won’t dive into each of them, but if you want to do more research, here are some examples.
For the calcification inhibitors, there’s…
Not surprisingly, studies have linked each of these “inducers” to hair loss… but no one’s yet identified their relationships to calcification.
he also argues regarding fibrosis which is a separate issue, is just as negative.. .... see no2 but go to the site as there is a lot more...
no 1 is the following https://www.sciencedirect.com/science/article/pii/0006291X89922389
Prostaglandin D2 stimulates calcification of human osteoblastic cells
Abstract
Studies on prostaglandin (PG) regulation of bone formation and resorption metabolism have been complicated by the heterogeneity of the tissue, which involves the interaction between and the activities of two bone cell types, osteoblasts and osteoclasts. In a simplified assay system using a cultured human osteoblastic cell line which has the capacity to form calcified tissue, we determined the effects of PGs on calcification. Of the PGs tested, PGD2 has a remarkable stimulatory activity on osteoblast calcification, but that the effective form is probably a metabolite, Δ12-PGJ2. This calcification function is not cAMP-mediated. PGD2 acts directly on osteoblast to cause stimulation of calcification.
----------------------------------------------------------------
no 2
https://perfecthairhealth.com/the-ultimate-hair-loss-flowchart-why-we-lose-our-hair/
What Is Calcification?
According to medical experts, calcification is “when calcium builds up in places where it doesn’t usually appear, like the coronary arteries or brain.”
Since elderly people often have more calcification, researchers once thought this process was a part of normal aging. But it turns out the relationship between age and calcification doesn’t really exist. Calcification doesn’t have to increase with age. It can be rampant in young adults and nearly absent in older ones.
And finally, it’s also important to note that calcification is not necessarily caused by a calcium-rich diet.
So back to our flowchart. Does calcification cause fibrosis?
Probably not. Most research suggests that calcification and fibrosis can occur in the same areas, but are likely independent of each other. And while some scleroderma patients also suffer from soft tissue calcification, others just suffer from an overproduction of collagen. So calcification does not have to happen before fibrosis and vice-versa.
Knowing this, we’re ready to add calcification into our flowchart. For simplicity’s sake, we’ll remove the visuals describing a balding scalp – the “thicker, tighter, shinier skin.”
Now let’s start tracing this chart backwards. We’ve gone as far as calcification and fibrosis. So what triggers both?
Calcification And Fibrosis Precede Hair Loss…
…But What Causes Calcification And Fibrosis?
We can get an idea of what might be causing these conditions if we look at the people most likely to develop arterial calcification and fibrosis: men.
Men are almost twice as likely as women to develop calcified arterial lesions. Why is that? Researchers have long suspected that androgens might be to blame. Read: testosterone and DHT – or dihydrotestosterone.
Why is this so interesting?
Well, most doctors agree that DHT causes hair loss… But none actually know how DHT causes hair loss. If DHT triggers calcification and fibrosis, this explains how DHT causes hair loss. But to confirm this, we need to know if androgens (like DHT) actually precede arterial calcification and fibrosis.
The DHT-Calcification-Fibrosis Connection
Does DHT Cause Calcification And Fibrosis?
Research here is mixed.
On the one hand, men and women who take androgens (steroids) significantly increase their risk of arterial calcification. And in mice, DHT and testosterone injections increase arterial calcification lesions by 200-400%. The more DHT or testosterone injected, the greater the calcification. That’s a pretty strong case that androgens cause calcification.
But paradoxically, in studies done in test tubes (outside of our bodies), increased androgens don’t cause calcification. In these tests, androgens protect against calcification.
This suggests two things:
- Androgens alone don’t cause calcification
- The test tube studies are missing at least one variable. It must be that increased androgens plus at least one “mystery variable” leads to calcification – but not androgens by themselves.
What does this suggest?
In the scalp, increased DHT plus these “mystery variables” precede both calcification and fibrosis. Knowing this, here’s our new flowchart:
So what could these mystery variables be?
Well, there are two. The first is an increase in androgen receptors. The second is an imbalance of calcification regulators. And explaining both are a bit of a mouthful. So bear with me.
A Crash Course On DHT, Androgen Receptors, And Calcification Regulators
We know that androgens alone don’t cause calcification, and that in the body, androgens must be interacting with other variables to cause calcification and fibrosis. So, what are those variables?
It appears there are two. And in 2016, researchers finally confirmed the first one: androgen receptors.
What Is An Androgen Receptor?
An androgen receptor (AR) is the place inside a cell where androgens – like testosterone and DHT – attach themselves. Think of an androgen receptor (AR) like the landing pad for DHT. Without its landing pad, DHT doesn’t bind to the cell.
Here’s a visual. This is a cell, and the yellow puzzle pieces (labeled AR) are androgen receptors:
(source)
Androgen receptors aren’t always active. They typically turn on in the presence of DHT or testosterone, then turn off when these hormones aren’t around.
The Connection Between Increased DHT And Increased Androgen Receptors
In our scalp tissues, increased androgens turn on more androgen receptors, and together, the increased DHT plus the increased androgen receptors results in calcification. Both DHT and androgen receptors must increase (not just one) for calcification to occur.
Interestingly, DHT plus androgen receptors also increase fibrosis in heart cells.
In other words, increased DHT + increased androgen receptors precede both calcification and fibrosis.
But here’s where things get tricky… Increased androgen receptors aren’t the only other variable. We know this because of DHT’s biggest paradox:
Increased tissue DHT encourages hair loss in the scalp, but encourages hair growth in the face and body.
That means that in our hairy facial and body tissues, calcification and fibrosis don’t occur. Why? Because in our bodies and face, increased DHT instead encourages hair growth – just the opposite of our scalps.
If our flowchart is accurate, this means that in the body and face, when DHT increases, androgen receptors must not increase. Otherwise, our body and facial tissues would also calcify, and hair wouldn’t grow.
But as it turns out, both balding scalps and hair-bearing body and facial tissues have increased DHT and increased androgen receptors… Yet hairy body and facial parts aren’t calcified or filled with fibrosis.
What does all of this mean?
In addition to DHT and androgen receptors, another factor must also be causing calcification and fibrosis. Either something is protecting our body and face from fibrosis and calcification, or something is causing both to happen in our scalps.
Taking this into account, here’s our new flowchart:
So, what is this new mystery variable? There are several contenders, but diving into all of them would turn this already-monstrous post into a full-blown book.
The reality is, we don’t yet know for sure.
The reason why: 99% of researchers still abide to the DHT-sensitivity argument. They say that “genetics” makes our hair follicles more sensitive to DHT, and that for unknown reasons, DHT accumulates in the scalp and eventually causes hair loss. To my knowledge, there are no current studies even exploring scalp DHT’s connection to calcification (even though when we look at broader research, the connection seems obvious).
On top of that, researchers only recently confirmed (in 2016!) that both an increase in androgens and androgen receptors are needed to cause calcification, not just one. This discovery came from cardiovascular researchers and not hair loss researchers. These fields don’t really talk to each other. Neither is very aware of the other’s work. As a result, our third mystery variable remains a mystery.
But even still, we can make a very strong case for what this variable could be.
Uncovering The New Mystery Variable
Here’s what we know: if we inject regular mice with DHT, they develop calcification. But if we inject DHT into mice who can’t produce androgen receptors, no calcification occurs. Why?
Let’s start by looking at the “engineered” mice who can’t express androgen receptors. When they receive DHT, their bodies respond by…
- Activating proteins associated with calcification inhibition
- Deactivating proteins associated with calcification induction
So how do the regular mice – the ones with androgen receptors – respond to a DHT injection? Just the opposite. When these mice receive DHT, their bodies…
- Turn on proteins that encourage calcium buildup
- Turn off proteins that usually suppress calcium buildup
This is important. Surrounding our bodies and facial hair, we don’t develop the same calcification or fibrosis that we see in balding regions of the scalp. The same isn’t true for our scalp hair. This suggests one thing:
Our new mystery variable is likely, among other things, an imbalance of calcification regulators.
What Are Calcification Regulators?
Calcification regulators are a set of (mostly) proteins with many names and functions. They regulate whether your tissues accumulate or release calcium. We won’t dive into each of them, but if you want to do more research, here are some examples.
For the calcification inhibitors, there’s…
- fetuin-A
- matrix gla protein
- osteopontin
- osteoprotegerin
- and dozens of others
Not surprisingly, studies have linked each of these “inducers” to hair loss… but no one’s yet identified their relationships to calcification.
Last edited:
