BB, look at this:
L8. Dihydrotestosterone (DHT)-inducible DICKKOPF 1 from scalp dermal papilla cells causes apoptosis in follicular keratinocytes.
Young-Kwar Sung, Mi-Hee Kwack, Moon-Kyu Kim, Jung-Chul Kim; Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
Paracrine factors induced by dihydrotestosteron (DHT) are thought to influence the activity of the follicular cells. RT-PCR analysis and ELISA showed that DICKKOPF 1 (DKK-1) is up-regulated and secreted to conditioned media upon DHT exposure. In addition, in vitro co-culture system by using dermal papilla cells (DPCs) and outer root sheath keratinocytes (ORS) showed that DHT inhibits ORS growth and neutralizing antibody against DKK-1 significantly attenuates DHT-induced growth inhibition of ORS cells. Flow cytometry analysis showed DHT induces substantial apoptosis in co-cultured ORS and caspase inhibitor attenuates DHT-induced growth inhibition of ORS. Altogether, this study shows that secreted DKK-1 from DPCs by DHT causes apoptosis in keratinocytes and suggests that DHT-inducible DKK-1 is responsible for the hair growth inhibition.
I have a few thoughts on this and what “baldness” might really come from and start out at. We know for a fact that the first inflammation seen in baldness is strangely near the infidulum, or the opening in the dermis where the hair comes out. It really seemed to make no sense to me (or anyone else) why that was, but now I think I see the correlation. The EHRS article above states that DHT-inductible DKK-1 leads to apoptosis (cell death) in keratinocyte cells. The speed of cell division in keratinocyte cells determines how “big” a hair follicle that one has. Hair growth only speeds up so much with treatments, and the speed at which the length of hairs grow out of the little “keratinocyte factory” which makes the long-cylinders of keratin that we know as “hair shafts” seems somewhat “fixed”. Fast cell division in the keratinocytes correlate with big, thick mature hairs.
Well then, if DKK-1 leads to “cell death” (apoptosis) directly in these cells, the [b-dead-cells are going to be “in there” with the keratinocytes, no doubt “break off” and travel along the hair shaft as it exits the infidulum (that ‘hole’ in the dermis where the hair departs). We have wondered openly for years on discussion forums as to “why does the immune system attack our hair” and why aren’t we like apes, who can get terrific regrowth out of finasteride, minox,and especially RU58841? We know that there is no immuno component to primate balding, but there is to ours (which is why its so hard to reverse vs. primates). I think I may see why the immune system attacks now. Its perfectly natural. The travelling T-cells that scavenge the body looking for “foreign invaders” would notice the dead keratinocyte cells a while after they were killed, but not before they completely leave the body. This would seemingly be why the immuno attack would first be noticeable at the infidulum. All the stuff that happens later, the collagen deposistion around the hair follicle, etc. might very well be the hair follicle trying to “defend” itself from the inflammatory acids, oxides, killer cells, etc. the immune system continually sends at the “foreign invader” near the top of the dermis.
You mentioned that caffeine was a wnt-upping substance, but what Im wondering is is topical caffeine just inhibits or binds DKK-1, http://search.comcast.net/?q=caffeine+dkk-1&cat=Web&con=preview?
I know that there is a big difference in alot of compounds before/after the enter the digestive system, and this is why caffeine might be of a topical benefit, but no internal benefit. Curcumin analogues are being developed by a company called Androscience to block androgen receptors and literally inhibit their very expression in targeted tissues, but internal curcumoids obviously dont do this—or eating curry would be like taking flutamide.
This makes me want to go back and re-look at the alpecin product and how it might be designed to work. I have found some more topical anti-androgens (DHT inhibitors) via this study:
Activity of herbal extracts on the control of sebum secretion.Accession number;04A0230063
Title;Activity of herbal extracts on the control of sebum secretion.
Author;UCHIUMI YOICHIRO(Maruzen Pharm. Co., Ltd., JPN) YAMAMOTO SUSUMU(Maruzen Pharm. Co., Ltd., JPN) MIZUTANI KENJI(Maruzen Pharm. Co., Ltd., JPN)
Journal Title;Fragr J
Abstract;Potential activity of herbal extracts on sebum secretion was studied. Among the herbal extracts tested, polyol-soluble licorice extract P-U (product name) derived from Glycyrrhiza inflata showed the most potent testosterone 5 .ALPHA.-reductase inhibition, androgen receptor binding inhibition and antimicrobial activities, which are closely related to sebum secretion. In addition to the findings on polyol-soluble licorice extract P-U, clove extract and peppermint extract showed testosterone 5 .ALPHA.-reductase inhibition, arnica extract and rose fruit extract showed androgen receptor binding inhibition, alpinia speciosa root extract and scutellaria root extract showed estrogen receptor agonists, and sophora root extract showed antimicrobial activity. (author abst.)
“Menthol” can be synthetic of course, but its been shown to inhibit alpha five reductase and decrease sebum in human skin. Alpecin has menthol, caffeine. I wonder if this is what they are up to…a topical anti-androgen, and an attempt to inbibit DKK-1 signalling so that keratinocytes dont “die” and induce and immunological response? I know that DKK-1 inhibits wnt signalling, and if we could stop it, wnt signalling might “start again” in the scalp to some extent, http://www.nature.com/onc/journal/v23/n52/abs/1207892a.html
It would seem if one were inclined to try the “needling” or whatnot, topical caffeine along with a DHT-inhibitor might be something to try anyway. BTW-anymore news on that front?
One more thingy…on one of the other anti-androgens mentioned in that Japanese study. Licorice, like green tea, inhibits angiogenesis or new blood vessel formation. At first glance it would seem that these should be whoop-ass anti-androgens, but I dont know if once could/or couldn’t induce terrific topical hair RE-growth by blocking new capillaries needed for the new hairs. I wonder. Do you know folks who claim great success with topical green tea? The ECGC should block androgen receptors and be quite anti-androgenic and in hamster flank organ studies it is incredibly effective against even topical DHT administration in keeping the flank organ from growing at all, even well over spironolactone.