As we have explained previously, RU58841 is a safe, effective cure for hair loss that acts by blocking the androgenic hormone dihydrotestosterone (DHT) from binding to receptors inside the cells of the hair follicle in the scalp. The adverse effect of DHT on the hair follicles of the scalp is completely unique to the scalp. Hair follicles in the face, chest, and other parts of the body are strongly stimulated to grow by DHT, which explains why men grow beards and chest hair, and women don’t. The reason why the scalp hair follicles respond differently to DHT in people with androgenic alopecia is still a mystery. Scientists have, however, been studying hair follicles, and are beginning to understand what is going on.
It All Starts with Dermal Papilla
During embryonic development, hair follicles develop fairly late in the gestation period through interactions between epithelial cells and mesenchymal cells. Scientists differentiate between different types of cells in the body. The cells that line or cover other parts are called epithelial cells. They are most familiar to people because they form the skin. Epithelial cells tend to form highly regular structures and also tend to not move much, preferring to attach to other epithelial cells and stay put. Mesenchymal cells, on the other hand, tend to form irregular structures, often secrete a lot of extracellular matrix material, and are prone to wandering. Most of the blood, joints, and bones are made out of mesenchymal cells. Anyway, back to hair follicles. A type of mesenchymal cell in the skin called a dermal papilla induces the epithelial cells to form a growth down and around the dermal papilla. Once encased inside the epithelial cells, the dermal papilla signals the epithelial cells to begin developing into a hair follicle and to grow hair.
One of the more interesting aspects of the development of the hair follicles is that the dermal papilla come from many different sources. For example, the dermal papilla that end up on the head come from the neural crest, while the dermal papilla that end up on the chest come from the lateral plate (1). These dermal papilla seem to “remember” their location of origin, which affects what genes they express even as they all turn into hair-follicle-inducing master cells. The source of the dermal papilla clearly affects how the final hair follicle responds to DHT-the androgen receptors in the scalp dermal papilla cells are what need to be blocked to prevent balding, but these same receptors are essential for chest hair growth.
The Hair Follicle Cycle
Hair follicles go through a defined cycle. Hair growth occurs during anagen, followed by a regression phase called catagen, and then a resting period that is referred to as telogen. During catagen, the epithelial cells in the hair follicle undergo apoptosis (programmed cell death) but the dermal papilla do not. Instead, they migrate up the hair follicle to lie just under the epithelial layer and remain there until the end of telogen. As anagen begins again, new epithelial cells start to grow and create a new hair follicle, and the dermal papilla migrate back down into the root area and start stimulating the epithelial cells to make more hair. However, in victims of androgenic alopecia, the hair follicles spend an abnormal amount of time in telogen, and sometimes they do not develop a full hair follicle as they re-enter anagen (the miniaturization process).
The Role of Wnt/Beta-catenin
A protein called Wnt has been shown to play a key role in the interactions between dermal papilla and epithelial cells during the hair follicle cycle. Wnt is a protein that is located on the surface of cells. When it is stimulated, it alters the expression of genes inside the cell. In a culture model of dermal papilla and hair follicles, when the dermal papilla were obtained from people with androgenic alopecia, the presence of androgens in the culture were found to inhibit the formation of the hair follicles (2). In the androgen treated dermal papilla, there was a significant decrease in the amount of beta-catenin in the cytoplasm and an increase in the activity of glycogen synthase kinase-3β, strongly suggested inhibition of the Wnt pathway. The scientists then went on to show that artificially stimulating the Wnt pathway in the dermal papilla was able to re-activate hair follicle formation. Therefore, in people with androgenic alopecia, androgens acting on the dermal papilla in the scalp prevent hair follicles from properly re-forming as they re-enter anagen through inhibition of Wnt signalling.
Premature Entry Into Catagen
In addition to having problems re-entering anagen, hair follicles in people affected by androgenic alopecia tend to prematurely enter catagen. This process has been shown to be mediated by a protein called Dickkopf 1 (DKK-1). In mice, treatment with DKK-1 protein induces the hair follicles to enter catagen, and blocking DKK-1 with special antibodies induces the hair follicles to remain in anagen (3). The effects of DKK-1 seem to be mediated through Wnt. When DKK-1 blocks Wnt signalling, the epithelial cells in the hair follicle are stimulated to undergo apoptosis, and the hair follicle enters catagen.
These findings suggest that there are several ways to treat androgenic alopecia-activate Wnt in the dermal papilla in the scalp, or block DKK-1 in the hair follicles in the scalp. Either approach should be able to keep the dermal papilla happily inducing the epithelial cells to grow hair. However, there are no effective, safe, easy-to-administer medications to accomplish either of the these feats. Simply blocking androgens from altering the dermal papilla of the scalp through the local application of RU58841 is currently the best way to take care of the dermal papilla and ensure that our hair grows.
(1) J Cell Sci. 2011 Apr 15; 124(8): 1179–1182. doi: 10.1242/jcs.082446 Hair follicle dermal papilla cells at a glance
(2) Br J Dermatol. 2012 May;166(5):1035-42. doi: 10.1111/j.1365-2133.2012.10856.x. Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia.
(3) Journal of Investigative Dermatology (2012) 132, 1554–1560; doi:10.1038/jid.2012.24; published online 23 February 2012 Dickkopf 1 Promotes Regression of Hair Follicles