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Increasing Vascular Endothelial Growth Factors (VEGF)

Vascular endothelial growth factor is one of the most important players that regulate vessel formation during embryonic development, in wound healing and in maintaining vessel homeostasis in adult organisms [3]. In addition, impaired vessel function resulting from defects in VEGF ligands or receptors is the cause of many diseases. Goldman and colleagues demonstrated that the expression of VEGF in human alopecia follicles significantly decreased comparing to the normal follicles [4]. Minoxidil, one of the pharmaceutical treatments approved for the therapy of AGA in men, could promote hair growth through upregulating the expression of VEGF in hair dermal papilla cells (DPC) [5]. Furthermore as an autocrine growth factor for hair dermal papilla cell, VEGF could stimulate the proliferation and migration of DPC [6]. Current data has shown that androgen receptor was expressed not only by vascular endothelial cells but also by DPC from balding as well as non-balding scalp [7]. And in different cell types, androgens may increase androgen receptor protein expression. By combining the above information, it is logical to propose that DHT may affect hair growth via VEGF/VEGFR. In vessels supplying the scalp, DHT binds to the androgen receptor of endothelial cells after the conversion of testosterone to DHT via 5a-reductase.

Afterwards, on the one hand, DHT reduces the production of VEGF resulting in less vascularization of hair follicle; on the other hand, DHT effects structural and anatomical changes in the vasculature, which result in diminished blood flow to the pilosebaceous unit and subsequently diminished hair growth. In hair follicle, the binding of DHT to androgen receptor down-regulate the expression of VEGF in DPC, shortening the duration of anagen and subsequently leading to hair loss.

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Lachgar S, Moukadiri H, Jonca F, et al. Vascular endothelial growth factor is an autocrine growth factor for hair dermal papilla cells. J Invest Dermatol 1996;106(1):17–23.

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Shin H, Yoo HG, Inui S et al. (2013) Induction of transforming growth factorbeta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells. BMB Rep 46:460–4

Su LH, Chen TH (2010) Association of androgenetic alopecia with metabolic syndrome in men: a community-based survey. Br J Dermatol 163:371–7

Tobin DJ, Gunin A, Magerl M et al. (2003) Plasticity and cytokinetic dynamics of the hair follicle mesenchyme: implications for hair growth control. J Invest Dermatol 120:895–904

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