One key factor in non-androgenic male pattern baldness is Dickkopf1 (DKK-1), which promotes catagen. It is suggested that DKK-1 blocks Wnt signaling by preventing β-catenin activation and instead activating the pro-apoptotic protein Bax, inducing apoptosis in outer root sheath keratinocytes. Current research supports that DKK-1 causes anagen to catagen induction leading to pattern baldness, which is commonly shown by older male populations [144].
The main cause of male pattern baldness in response to hormones or androgenic alopecia is due to dihydrotesterone, which is produced by balding dermal papillae. Presence of dihydrotesterone in HF occurs either through the DP capillaries, as it is normally circulated in the blood, or by conversion of testosterone in balding DP cells. Presence of dihydrotesterone causes upregulation of IL-6 that in turn promotes the expression of the IL-6 receptor along with glycoprotein 130 in keratinocytes and matrix cells. The outcome of this IL-6-upregulated expression is inhibition of the hair shaft elongation with simultaneous suppression of matrix cells proliferation. Studies in this regard have shown that IL-6 expression induces anagen-catagen progression [145].
Shh pathway is known to play an important role in both embryonic hair development as well as in the normal cycling of adult HF, and implies in the induction of anagen phase accompanied by hair growth [82]. Certain defects related to catagen HF arrest can be treated with the ectopic activation of Shh pathway that promotes catagen to anagen transition, restoring normal hair growth. However, caution must be taken, as excessive Shh activation can lead to skin cancer.
A few miRNAs have been implicated in male patterned baldness. Recent evidence has demonstrated upregulation of miR-221, miR-125b, miR-106a and miR-410 in balding papilla cells [146]. miRNAs have an established role in the functioning of androgenic receptors [147]. Androgen secretion affects hair color and size via the hair growth cycle. miR-221 targets functioning of receptor tyrosine kinase, c-kit, and the cyclin-dependent kinase inhibitors p27/kip1 and p57/kip2 [148]. miR-221 may impede SCF/c-kit signaling, which is involved in melanocyte migration and maintaining pigmentation. To date, no specific role has been assigned to these miRNAs, and further research is necessary to evaluate their upregulation in alopecia or male patterned baldness.
