Why Dr Peat advises to use DHEA Progesterone to grow hair

PeskyPeater

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Goodday!

"Hair loss, like obesity or hypertension, should be taken seriously, as an indication of a systemic metabolic problem. The metabolism of the hair follicle contains clues to aging, tissue regeneration, and cancer." -- Ray Peat

I can now begin to see why Dr Peat advises to use DHEA with Progesterone to grow hair.

The DHEA get's metabolized towards E1 Estrone ( and or E2 ) [6] which support the glycolytic 'cancerous like' state of hair growth that uses glutamine and glucose as a source that convert to lactate as inefficient form of energy for the hair follicle. [1]

Progesterone can inhibit increases in aromatase induced by cortisol, normalizing the endocrine function of the scalp caused by stress. [2]

PROG like DHEA, can mildly inhibit mitochondrial respiratory Complex I [5] that results in boosting the ETC to support new growth of hair from the hair follicle stem cells (in the hair bulge) by switching from glycolysis to aerobic respiration in those differentiated stem cells for a higher energy supply. [3]

And also helping to differentiate stem cell mitochondrial metabolism to let form new hair follicles in the scalp. [4]

[6] source
[ from the thread: estrogen-e1-more-important-for-hair-than-testosteron]
1660073745598.png

fcell-08-595178-g001.jpg

[1]
The human hair follicle engages in glutaminolysis and aerobic glycolysis: implications for skin, splanchnic and neoplastic metabolism - PubMed

Abstract​

On maintenance in supplemented Williams E medium, human hair follicles grow at the normal rate, and retain their normal anagen morphology, for up to 10 days. This permits us to study their metabolism under near-physiological conditions. The ATP content of freshly isolated follicles was 124.4 +/- 10.6 pmol/follicle (mean +/- SEM; n = 50). The energy charge was 0.81 +/- 0.08 and the glycogen content 2.3 +/- 0.3 nmol/follicle. These did not alter significantly during any metabolic studies, which were performed for up to 6 h in supplemented Williams E medium. We found that the major fuel was glucose, which at physiological concentrations yields 5.47 +/- 0.77 nmol ATP/follicle/h, but 90% of the glucose was metabolised to lactate, and only 10% oxidised. Glutamine was also an important fuel, generating 2.16 +/- 0.33 nmol ATP/follicle/h, but this too was largely metabolised to lactate rather than oxidised. Lipid fuels such as palmitate or beta-hydroxybutyrate only yielded 0.72 +/- 0.15 and 0.72 +/- 0.14 nmol ATP/follicle/h, respectively, and their oxidation did not inhibit glucose utilisation. No glucose-fatty acid cycle operates in the hair follicle, therefore, but a glucose-glutamine cycle does, since the presence of glutamine will inhibit glucose utilisation.
[2] https://joe.bioscientifica.com/downloadpdf/journals/joe/158/3/401.xml
Results
Aromatase induction in human adipose fibroblasts is observed after treatment with either [fetal calf serum] FCS or [Platelet-derived growth factor ]PDGF-BB in the presence of cortisol. To test the influence of progesterone on estrogen biosynthesis in adipose tissue, adipose fibroblasts were incubated with various concentrations of progesterone immediately before aromatase was induced by addition of cortisol together with either FCS or PDGF-BB. With progesterone in concentrations ranging from 100 nM to 10 µM, aromatase induction was inhibited in a dosedependent manner. When FCS was used instead of PDBF-BB as a mediator of aromatase induction, the dose–response curve was shifted to the right. About fivefold higher progesterone concentrations are needed to obtain a degree of inhibition comparable to that observed in the presence of PDGF-BB (Fig. 1A and B). When 0·1 µM cortisol was used together with 0·5 nM PDGF-BB, the aromatase activities were reduced to about 80% of those seen after treatment of cells with 1 µM cortisol. Under these conditions, progesterone was more effective, resulting in almost complete inhibition of aromatase at a concentration as low as 0·1 µM. In the absence of cortisol, there was no effect of progesterone on aromatase induction with either FCS or PDGF-BB. Release of lactate dehydrogenase and alkaline phosphatase from the cells does not change during the culture period upon treatment with 10 nM to 10 µM progesterone (data not shown). Therefore progesterone does not affect overall cell performance, but interacts specifically with the glucocorticoid-dependent pathway of aromatase induction.
[3]
https://www.researchgate.net/public...and_its_dysfunction_retards_hair_regeneration
Results. During HFSCs differentiation, mitochondria became elongated with more
abundant organized cristae and showed higher activity in differentiated cells. SOD2
was enhanced for redox balance with relatively stable ROS levels in differentiated
cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH,
indicating that respiration switched from glycolysis to oxidative phosphorylation during
differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells
upon hair plucking repressed hair regeneration in vivo.
Conclusions. Upon HFSCs differentiation, mitochondria are elongated with more
abundant cristae and show higher activity, accompanying with activated aerobic
respiration in differentiated cells for higher energy supply. Also, dysfunction of
mitochondrial respiration delays hair regeneration upon injury.
[4] A novel and safe small molecule enhances hair follicle regeneration by facilitating metabolic reprogramming - Experimental & Molecular Medicine

Abstract​

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.

[5] Dehydroepiandrosterone inhibits complex I of the mitochondrial respiratory chain and is neurotoxic in vitro and in vivo at high concentrations - PubMed
The observed effect of DHEA on complex I activity and mitochondrial respiration was specific not only for this compound but also for some other neurosteroids. Progesterone inhibited complex I at similar concentrations as DHEA (IC50 39 ± 3lM), pregnenolone (IC50 90 ± 24lM), and estradiol (IC50 116 ± 3lM) were weaker, and DHEAS and cholesterol (IC50 > 350lM) were ineffective. Also, the DHEA metabolites 7-alphahydroxy-DHEA, 7-beta-hydroxy-DHEA, and 7-keto-DHEA, were ineffective (IC50 between 290 and 360lM).
 
Last edited:
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Blaze

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Goodday!



I can now begin to see why Dr Peat advises to use DHEA with Progesterone to grow hair.

The DHEA get's metabolized towards E1 Estrone ( and or E2 ) [6] which support the glycolytic 'cancerous like' state of hair growth that uses glutamine and glucose as a source that convert to lactate as inefficient form of energy for the hair follicle. [1]

Progesterone can inhibit increases in aromatase induced by cortisol, normalizing the endocrine function of the scalp caused by stress. [2]

PROG like DHEA, can mildly inhibit mitochondrial respiratory Complex I [5] that results in boosting the ETC to support new growth of hair from the hair follicle stem cells (in the hair bulge) by switching from glycolysis to aerobic respiration in those differentiated stem cells for a higher energy supply. [3]

And also helping to differentiate stem cell mitochondrial metabolism to let form new hair follicles in the scalp. [4]

[6] source
[ from the thread: estrogen-e1-more-important-for-hair-than-testosteron]
View attachment 40232
fcell-08-595178-g001.jpg

[1]
The human hair follicle engages in glutaminolysis and aerobic glycolysis: implications for skin, splanchnic and neoplastic metabolism - PubMed

[2] https://joe.bioscientifica.com/downloadpdf/journals/joe/158/3/401.xml

[3]
https://www.researchgate.net/public...and_its_dysfunction_retards_hair_regeneration

[4] A novel and safe small molecule enhances hair follicle regeneration by facilitating metabolic reprogramming - Experimental & Molecular Medicine


[5] Dehydroepiandrosterone inhibits complex I of the mitochondrial respiratory chain and is neurotoxic in vitro and in vivo at high concentrations - PubMed
Thank you for all that info................ very interesting stuff
 

Motorneuron

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One thing comes to mind looking at many bodybuilders today ... hair loss and "older" face could indicate a drop in progesterone levels at this point 🙂 .... given the huge doses of testosterone and even aromatase inhibitors.
 
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PeskyPeater

PeskyPeater

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Thank you for all that info................ very interesting stuff
you are welcome!
One thing comes to mind looking at many bodybuilders today ... hair loss and "older" face could indicate a drop in progesterone levels at this point 🙂 .... given the huge doses of testosterone and even aromatase inhibitors.
I think you make a good point there. Testosterone replacement therapy may lower progesterone. And some aromatase inhibitors causing estrogen deprivation can make cells hypersensitive to oestrogens.
 
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PeskyPeater

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Dr Peat also advised to use 'carbonic anhydrase inhibitors' for hair growth. He mentioned Silymarin and Curcumine. What's that about?

I think this following study is meaningful. Using acetazolamide changed the metabolism of mitochondria.
It seems inhibitors of CA can result in increased lactate which is a substrate for the hair follicle.


Carbonic anhydrases are involved in mitochondrial biogenesis and control the production of lactate by human Sertoli cells​


Raquel L. Bernardino,Tânia R. Dias,Bruno P. Moreira,Mariana Cunha,Alberto Barros,Elsa Oliveira,Mário Sousa,Marco G. Alves,Pedro F. Oliveira
First published: 06 February 2019

https://doi.org/10.1111/febs.14779
Citations: 11

Abstract​


The process that allows cells to control their pH and bicarbonate levels is essential for ionic and metabolic equilibrium. Carbonic anhydrases (CAs) catalyse the conversion of CO2 to
urn:x-wiley:1742464X:media:febs14779:febs14779-math-0001
[HCO3-]and H+ and are thus essential for this process. Herein, we inhibited CAs with acetazolamide – ACT and SLC-0111 – to study their involvement in the metabolism, mitochondrial potential, mitochondrial biogenesis and lipid metabolism of human Sertoli cells (hSCs), obtained from biopsies from men with conserved spermatogenesis. We were able to identify three isoforms of CAs, one mitochondrial isoform (CA VB) and two cell membrane-bound isoforms (CA IX and CA XII) in hSCs. When assessing the expression of markers for mitochondrial biogenesis, we observed a decrease in HIF-1α, SIRT1, PGC1α and NRF-1 mRNAs after all CAs were inhibited, resulting in decreased mitochondrial DNA copy numbers. This was followed by an increased production of lactate and alanine in the same conditions. In addition, consumption of glucose was maintained after inhibition of all CAs in hSCs. These results indicate a reduced conversion of pyruvate to acetyl-coA, possibly due to decreased mitochondrial function, caused by CA inhibition in hSCs. Inhibition of CAs also caused alterations in lipid metabolism, since we detected an increased expression of hormone-sensitive lipase (HSL) in hSCs. Our results suggest that CAs are essential for mitochondrial biogenesis, glucose and lipid metabolism in hSCs. This is the first report showing that CAs play an essential role in hSC metabolic dynamics, being involved in mitochondrial biogenesis and controlling lactate production. https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14779
 

Motorneuron

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you are welcome!

I think you make a good point there. Testosterone replacement therapy may lower progesterone. And some aromatase inhibitors causing estrogen deprivation can make cells hypersensitive to oestrogens.
Forgive the digression but during the TRT or AAS cycle could they not suggest a combination of DHEA and / or progesterone along with testosterone in order to keep the hypothalamus pituitary testis axis active? or is it just a utopia? Is it possible that only HCG, Nolvadex and clomid work?
 
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PeskyPeater

PeskyPeater

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Forgive the digression but during the TRT or AAS cycle could they not suggest a combination of DHEA and / or progesterone along with testosterone in order to keep the hypothalamus pituitary testis axis active? or is it just a utopia? Is it possible that only HCG, Nolvadex and clomid work?
wow too much information. I am not a doctor. Would work to do what?
I would suggest using progesterone with TRT.
 

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