OK We So Know Prostaglandin D2 Is The Main Driver Behind Baldness. What Can We Do About It?

Travis

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Jul 14, 2016
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@Travis might find this one interesting re: baldness, acne, cancer

Int J Mol Sci. 2018 Feb 12;19(2). pii: E556. doi: 10.3390/ijms19020556.
Prostaglandin D2-Mediated DP2 and AKT Signal Regulate the Activation of Androgen Receptors in Human Dermal Papilla Cells.
Jeong KH1, Jung JH2, Kim JE3, Kang H4.

Prostaglandin D2 (PGD2) and prostaglandin D2 receptor 2 (DP2) is known to be an important factor in androgenetic alopecia (AGA). However, the effect of PGD2 in human dermal papilla cells (hDPCs) is not fully understood. The function of PGD2-induced expression of the androgen receptor (AR), DP2, and AKT (protein kinase B) signal were examined by using real time-PCR (qRT-PCR), western blot analysis, immunocytochemistry (ICC), and siRNA transfection system. PGD2 stimulated AR expression and AKT signaling through DP2. PGD2 stimulated AR related factors (transforming growth factor beta 1 (TGFβ1), Creb, lymphoid enhancer binding factor 1 (LEF1), and insulin-like growth factor 1, (IGF-1)) and AKT signaling (GSK3β and Creb) on the AR expression in hDPCs. However, these factors were down-regulated by DP2 antagonist (TM30089) and AKT inhibitor (LY294002) as well as DP2 knockdown in hDPCs decreased AR expression and AKT signaling. Finally, we confirmed that PGD2 stimulates the expression of AR related target genes, and that AKT and its downstream substrates are involved in AR expression on hDPCs. Taken together, our data suggest that PGD2 promotes AR and AKT signal via DP2 in hDPCs, thus, PGD2 and DP2 signal plays a critical role in AR expression. These findings support the additional explanation for the development of AGA involving PGD2-DP2 in hDPCs.

That's an interesting abstract. It appears that the author is aiming to take the sum undeniable evidence implicating prostaglandin D₂ in hair loss and fit it inside of the androgenic paradigm, perhaps trying to synthesize a unified über-theory or merely trying to 'save the hypothesis'—this being unsavable however, considering the findings of Valeria Randall and others. Nonetheless, this is a good find and I do plan on reading it; it's good to know about all new prostaglandin research.

"Popper maintains that he can distinguish between modifications of hypotheses which are "permissible" from those which are purely ad hoc, and according to his methodology, prohibited. Permissible moves are those which render the whole conjunction of hypotheses and auxiliary assumptions more testable; those which do not lead to new testable consequences but function only to "save" the hypothesis supposedly under test are ad hoc and outlawed by the logic of science. The epistemologist essentially prescribes methodology to the scientist in this respect." ―Folse

But if prostaglandin D₂ were to act primarily through the induction of the androgen receptor, it would then be expected to increase hair growth in the scalp⁽¹⁾—as androgens obviously do this everywhere else. But prostaglandin D₂ does not do this, it causes hair loss when applied directly, so androgen receptor induction is unlikely to be its primary function. But I do think this gives a good explanation for why androgen receptors have been found to be slightly elevated in hairless regions.⁽²⁾

I was thinking about nitric oxide and cyclooxygenase, and that perhaps even prostaglandin D₂ could be somewhat secondary. Nitric oxide is a confirmed vasodilator, yet it can paradoxically restrict blood flow in the smaller capillaries simply through the dilatation of the larger. It has also been shown to catalyze the formation of prostaglandin H directly by acting on cyclooxygenase, as a substrate: The endoperoxide ring characteristic of the the entire class of prostaglandins can be initially formed from peroxynitrite, this being a ṄO–superoxide fusion. I don't think the ability of nitric oxide to powerfully catalyze prostaglandin synthesis should be ignored, and that an increase if prostaglandin D₂ observed in hairless regions would have necessarily been proceeded by a corresponding increase of nitric oxide—which is known cause the actual constriction of fine capillaries. But then again: It cannot be argued that prostaglandin D₂ has powerful signalling effects of its own, and some of these effects are also vasoactive. Prostaglandin D₂ has been shown to be vasopressive in some experiments, directly in opposition to prostaglandin E₂'s effect on the arteries (these two appear oppositional on many levels). So prostaglandin D₂ could logically be expected to constrict blood vessels—perhaps even having the intent of homeostatically countering the vasodilation induced by the same molecule, nitric oxide, which accelerates its formation.


[*] (via peroxynitrite)
[1] Randall, V. "Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo." Journal of investigative dermatology (1992)
[2] Hibberts, N. "Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp." Journal of Endocrinology (1998)
 
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Hairfedup

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Dec 3, 2017
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all you guys can have super thick nw1 hair with 80mg sustanon e6d and 250iu hcg 2x a week with 0.25 arimidex and 0.5mg finasteride 2-3 times a week this will improve your t-e ratio which is the main reason of hairloss and diet should be high carb extremly low fat and person should be lean 15%bf at most. I myself will be starting this protocol within a week.will be updating you guys.

Bro you sound very sure of yourself and I really hope it works for you, but how can you know this will work? Sounds like a recipe for disaster...added to the fact that its most likely PGD2 and not an androgenic issue?
 

restinpeace

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Sep 18, 2017
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why did you say recipe for disaster?Estrogen is really bad for males and dht causes hairloss in excess if testosteron-estrogen ratio is bad, dht itself is good for hair if it is in acceptable normal range.I also think high estrogen causes body hair growth and hypersexuality by upregulating dht and other androgens or it makes dht super effective basically sensitizes androgen receptors most people on finasteride reports high libido and oily skin acne thats due to increased estrogen ı myself become hypersexual masturbating a lot when ı was on 1.25mg finasteride everyday.if you arent willing to take risk for you hair just consider aromasin 6.5mg e3d and finasteride 0.5 or 1.25mg e3d it takes 4-5 days for dht to rise again.
 

MrSmart

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Jul 9, 2018
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139
So‐called 'androgenic' alopecia is less prevalent in Korea, by quite a bit:

View attachment 8442

But this cannot be 'androgenic,' because many Koreans have a 'female hair loss pattern.' This is characterized by the retention of hair curcumscribing the hairline, 360°, with only diffuse crown thinning.

'In Korean men, the prevalence of AGA (Norwood III or above) at all ages was 14.1%. It increased steadily with advancing age, but was lower than that of caucasians: 2.3% in the third decade, 4.0% in the fourth decade, 10.8% in the fifth decade, 24.5% in the sixth decade, 34.3% in the seventh decade and 46.9% over 70 years. Type III vertex involvement was the most common type in the third decade to the seventh decade; over 70 years, type VI was most common. A `female pattern' was observed in 11.1% of cases. In Korean women, the prevalence of AGA (Ludwig I or above) [?] at all ages was 5.6%. It also increased steadily with advancing age: 0.2% in the third decade, 2.3% in the fourth decade, 3.8% in the fifth decade, 7.4% in the sixth decade, 11.7% in the seventh decade and 24.7% over 70 years.' ―Paik

So not only do Koreans have less hair loss, what they do lose is lost in a way similar to females. I think this makes sense if you think about their ω−6/ω−3 ratios and perhaps relative lack of stress. Nonetheless, Koreans aren't perfect and still consume linoleic acid and some no doubt have stressful lives (think Fukushima; fish prices; ect.).

The authors attempt to explain this, of course, by genetics; they do this in spite of absolutely no proof. While its' true that Asians' hair differs bit, perhaps having slight keratin polymorphisms (known to effect hair curl in animals), African Americans have similar hair and lose it to a greater extent. Also, many caucasians also have smooth black hair.

'However, analysis of candidate genes for AGA by restriction fragment length polymorphism found no genetic variation in the 5α-reductase type 1 gene or the 5α-reductase type 2 gene or their regulation.' ―Paik

These types of studies of course totally demolish the idea that hair loss is dose-dependent on androgens. I have maintained that DHT only contributes to the extent that it acts on the thymus and the adrenals, two organs with a high-density of androgen receptors. For this reason, males have both a higher cortisol output on average and differential immune parameters (i.e. lower INF-γ). After all, it must work somewhere; dihydrotestosterone actually increases hair growth at the folliclle. The fact that DHT works circuitously through cytokines and cortisol also helps to explain why spironolactone and cyclosporine are more effective than finasteride.

I am willing to bet that Israeli men have the highest prevalence of alopecia simply on account the their extremely high ω−6/ω−3 ratio.

Paik, J‐H. "The prevalence and types of androgenetic alopecia in Korean men and women." British Journal of Dermatology (2001)

Don't you mean higher INF-γ?

And you haven't really explained the reason behind the FPHL according to your cytokine/PGD2 theory in the Korean population.

 
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