It never ceases to amaze me how many people are still convinced that DHT is “the” cause of hair loss, and if we address it, our hair loss worries will be over. If that were true, Propecia would have given us all Brad Pitt hair lines, and we could have happily gone about our business in 1998 when it was “approved.” Unfortunately, hormone driven hair loss is a bit more complex than that. The good news is that our expanding knowledge of the complex factors involved have produced an array of viable treatment targets and interventions, and that any results one may get or already have from blocking or inhibiting the production DHT can be significantly enhanced.
Inflammation and eventual fibrosis, in addition to DHT have been conclusively implicated in the pathogenesis of autoimmune and hormonal pattern hair loss in both genders, and ultimately play a more direct role than DHT in the gradual miniaturization of the hair follicle. Any hair loss treatment approach generally needs to take inflammation and fibrosis into account to have any real chance of a cosmetically significant, sustainable result.
Specific components of inflammation and fibrosis that contribute to hormonal hair loss (MPB) have been identified, and provide viable targets for intervention. Among these are TGF-Beta and Caspase 1. Shiseido, a large Japanese cosmetic company, has been on the forefront of researching the role of inflammation in Androgenetic Alopecia.
J Dermatol Sci. 2004 Jun;35(1):9-18.
Role of TGF-beta2 in the human hair cycle.
Hibino T, Nishiyama T.
Shiseido Life Science Research Center, 2-12-1 Fukuura, Kanazawa-ku, Yokohama 236-8643, Japan.
Male pattern baldness is the result of premature entry into catagen due to androgens. In order to prevent hair loss, it is important to understand two critical steps, i.e., the induction mechanism of premature entry and the regression process of catagen. At the initiation, dihydrotestosterone (DHT) stimulates synthesis of transforming growth factor-beta2 (TGF-beta2) in dermal papilla cells. TGF-beta2 suppresses proliferation of epithelial cells and stimulates synthesis of certain caspases. Then TGF-beta2 triggers the intrinsic caspase network and subsequently epithelial cells are eliminated through apoptotic cell death. TGF-beta antagonists are effective in preventing catagen-like morphological changes and in promoting elongation of hair follicles in vivo and in vitro.
These lines of evidence strongly suggest the presence of a “catagen cascade” in male pattern baldness, involving: (1) the conversion of testosterone to DHT by type II 5-alpha-reductase; (2) the synthesis of TGF-beta2 in dermal papilla cells; and (3) the activation of the intrinsic caspase network. These sequential events contribute to the shortening of the human hair cycle.
Not surprisingly, the research team from Shiseido found that suppressing TGF-Beta, prevented the progressive miniaturization seen in MPB.
A potential suppressor of TGF-beta delays catagen progression in hair follicles.
Tsuji Y, Denda S, Soma T, Raftery L, Momoi T, Hibino T.
Shiseido Life Science Research Center, Yokohama, Japan.
TGF-beta plays important roles in the induction of catagen during the hair cycle. We examined whether TGF-beta2 could activate a caspase in human hair follicles. Using active caspase-9 and -3 specific antibodies, we found that TGF-beta2 activated these caspases in two regions, the lower part of the hair bulb and the outer layer of the outer root sheath. In addition, we searched for a plant extract that can effectively suppress TGF-beta action. We found that an extract of Hydrangea macrophylla reduced synthesis of a TGDbeta-inducible protein. We confirmed that the extract has a potential to promote hair elongation in the organ culture system. Furthermore, it delayed in vivo progression of catagen in a mouse model. Our results suggest that the induction of catagen by TGF-beta is mediated via activation of caspases and that a suppressor of TGF-beta could be effective in preventing male pattern baldness.
In addition to the extract being developed by Shiseido mentioned above, TGF Beta, fibrosis, and other inflammatory components of hair loss have been targeted by several biotech and cosmetic companies, (most notably, L’Oreal), with patented, health promoting interventions that are documented to produce hair growth. Chief among these are:
Inflammation that contributes to hair loss can also be at least partially favorably impacted by dietary intervention: