Im going to cut-and-paste a post from the RSG (Real Smart Guy) Harold from over at hlt. He’s very bright and well-read. These are his thoughts on how Follica might work theoretically:
Maybe I should have put this in the follica thread but oh well.
EGF inhibitors can cause slower scalp hair growth and longer eyelash growth… But EGF overexpression seems to mess with hair cycling. Slows it down.
J Invest Dermatol. 2008 May;128(5):1256-65. Epub 2007 Oct 25.Click here to read Links
Betacellulin regulates hair follicle development and hair cycle induction and enhances angiogenesis in wounded skin.
Schneider MR, Antsiferova M, Feldmeyer L, Dahlhoff M, Bugnon P, Hasse S, Paus R, Wolf E, Werner S.
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Munich, Germany. email@example.com
Betacellulin (BTC) belongs to the EGF family, whose members play important roles in skin morphogenesis, homeostasis, and repair. However, the role of BTC in skin biology is still unknown. We employed transgenic mice overexpressing BTC ubiquitously to study its role in skin physiology. Immunohistochemistry revealed increased levels of BTC especially in the hair follicles and in the epidermis of transgenic animals. Expression of key markers of epithelial differentiation was unaltered, but keratinocyte proliferation was significantly increased. At post-natal day 1 (P1), transgenic mice displayed a significant retardation of hair follicle morphogenesis. At P17, when most follicles in control mice had initiated hair follicle cycling and had already entered into their first late catagen or telogen phase, all follicles of transgenic mice were still at the mid- to late catagen phases, indicating retarded initiation of hair follicle cycling. Healing of full-thickness excisional wounds and bursting strength of incisional wounds were similar in control and transgenic mice. However, an increase in the area covered by blood vessels at the wound site was detected in transgenic animals. These results provide evidence for a role of BTC in the regulation of epidermal homeostasis, hair follicle morphogenesis and cycling, and wound angiogenesis.
I’m not gonna pretend to be on top of everything that this abstract mentions but a lot of those targets of EGF interact very strongly with wnt/BMP signalling pathways indicating some kind of convergence.
Mol Cell Biol. 2006 Aug;26(16):6283-98.Click here to read Click here to read Links
Selective modulation of Hedgehog/GLI target gene expression by epidermal growth factor signaling in human keratinocytes.
Kasper M, Schnidar H, Neill GW, Hanneder M, Klingler S, Blaas L, Schmid C, Hauser-Kronberger C, Regl G, Philpott MP, Aberger F.
Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria.
Hedgehog (HH)/GLI signaling plays a critical role in epidermal development and basal cell carcinoma. Here, we provide evidence that epidermal growth factor receptor (EGFR) signaling modulates the target gene expression profile of GLI transcription factors in epidermal cells. Using expression profiling and quantitative reverse transcriptase PCR, we identified a set of 19 genes whose transcription is synergistically induced by GLI1 and parallel EGF treatment. Promoter studies of a subset of GLI/EGF-regulated genes, including the genes encoding interleukin-1 antagonist IL1R2, Jagged 2, cyclin D1, S100A7, and S100A9, suggest convergence of EGFR and HH/GLI signaling at the level of promoters of selected direct GLI target genes. Inhibition of EGFR and MEK/ERK but not of phosphatidylinositol 3-kinase/AKT abrogated synergistic activation of GLI/EGF target genes, showing that EGFR can signal via RAF/MEK/ERK to cooperate with GLI proteins in selective target gene regulation. Coexpression of the GLI/EGF target IL1R2, EGFR, and activated ERK1/2 in human anagen hair follicles argues for a cooperative role of EGFR and HH/GLI signaling in specifying the fate of outer root sheath (ORS) cells. We also show that EGF treatment neutralizes GLI-mediated induction of epidermal stem cell marker expression and provide evidence that EGFR signaling is essential for GLI-induced cell cycle progression in epidermal cells. The results suggest that EGFR signaling modulates GLI target gene profiles which may play an important regulatory role in ORS specification, hair growth, and possibly cancer.
OK I think a big action of androgens in the skin is that they promote sebaceous gland growth more or less everywhere and retard hair follicle formation on the scalp. Epidermal stem cells are in a state (roughly) where they can become sebaceous glands, hair follicles or skin cells. Wnt signalling is one of the things that biases a stem cell to become a ahir follicle rather than a sebaceous gland or skin cell. Wnt and DKK1 are 2 molecules that seem to determine hair follicle spacing in the scalp according to a reaction diffusion principle - this forms a natural pattern much like spots on a leopard, stripes on a zebra - not too random, not too regular. One of the notes from the first Cotsarelis wounding patent was constantly talking about a method to induce hair growth by bringing a hair follicle or portion thereof or an inductive cell close to the uncomitted epidermal cell to convince it to become a hair follicle. I think this is because as animals are furry all over when you wound them they have more of a tendency to grow fur back. The same would be true of a hairy persons scalp. But i think if you tried wounding your palm you wouldnt grow any hairs back partly because there would be alot of DKK1 floating around and partly because these stem cells seem to take cues from their neighbours as to what they should differentiate into. I think this is why its easier to regrow on a thinning vertex than temples. Less interference from the neighbours. But EGF inhibition probably overcomes that inhibition.
Mucking with BMP/Wnt signalling seems to promote sebaceous gland enlargement at the same time as inhibiting hair follicle growth . I think this is very important. This is one of the key things that separates MPB from alopecia areata and other hair loss conditions. Its practically synonymous with androgenic effects in the scalp.
There are many mouse models of alopecia that dont apply to MPB that well. However when mice overexprssed COX-2 in the skin they developed sparse coats of thinning hair. That hair was also greasy due to sebaceous gland enlargement. Importantly the hair loss could be prevented by using a COX inhibitor but seemingly could not be reversed. Much like MPB hair loss and antiandrogens.
When Cotsarelis found the elevation in prostaglandin D2 in bald scalp someone was canny enough to remember this model and make the connection between increased prostaglandin production in mouse skin. Looking at it they saw that PGD2 was through the roof in the skin of these mice. Inhibiting prostaglandin d2 could reverse the sebaceous gland growth and prevent the loss of hair. Though this is very suggestive it is not an airtight case yet by any means. One would have to show cause and effect in humans between PGD2 and hair loss. Not just correlation. That would take a trial. And trials take at least about 6 months let alone writing up etc.
At any rate I think it suggests that PGD2 messes with the balance of wnt/bmp/dkk1 in the skin and what would have become hair follicles start to thin while sebaceous glands become fat…
anyway I have digressed. I may have even written this before but it was in my head and i had to get it out