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)