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Insulin-Like Growth Factor (IGF-1)

Scientific Review by Dr. Luna, MD
Medical Director, Roots Hair Club

IGF-1 is one of the important mechanisms contributing to male pattern baldness. Of all the cytokines or growth factors that have been postulated to play a role in hair follicle, insulin-like growth factor- 1 (IGF-1) is arguably the most studied, has an essential role in hair cycle control as well as hair shaft differentiation during the development of hair follicles and its known to be regulated by androgens(1). Produced by mesenchymal Dermal Papila cells, inhibits apoptosis and promotes epithelial cell growth. Is a physiologic regulator of hair growth cycle and helps maintain anagen stage(2)

It has been shown that Dermal Papila cells from balding scalp follicles secrete significantly less IGF-1, IGFBP-2 and IGFBP-4 (P < 0.05) than their non-balding counterparts. The data confirmed that the downregulation of IGF-1 may be one of the important mechanisms contributing to male pattern baldness.

IGF-1 has been reported to promote hair follicle growth in vitro by regulating cellular proliferation.

In the absence of IGF-1 or insulin, anagen hair follicles in organ culture enter catagen [2]. Furthermore, IGF-1 receptor knockout mice show a marked decrease in the absolute number of hair follicles, abnormal hair follicular pattern and hair differentiation. IGF is also a candidate for androgen-induced hair growth factor. This is supported by increases in the levels of IGF-1 and insulin-like growth factor-binding proteins (IGFBPs) in beard DP cells. However, how IGF-1 is altered in the balding scalp has not been investigated.

The expression of IGF-1 in the dermal papilla is discussed to play an important role in the development of pattern balding. Older men with vertex balding showed higher plasma levels of IGF-1 and lower circulating levels of IGF binding protein (3). A decreased expression of IGF-1 was found in the balding scalp tissue. The gene locus for IGF-1 can be found on chromosome 12 (12q22-q23)

Theoretically, treatments that can stimulate the secretion of IGF-1 may slow hair loss. IGF-1 has also been shown to be upregulated in DP cells of patients with AGA who respond to finasteride. (4)

Insulin-like growth factor-binding proteins comprise a family of six related peptides that compete with IGF receptors for binding. They can affect cell growth, differentiation and survival by either IGF-dependent or IGF-independent effects. Every IGFBP is expressed in a tightly regulated manner both time and tissue specific, signifying that each protein may have its own distinct functions. IGFBP-2 acts mainly by inhibition of IGF bioactivity demonstrated in vitro studies and transgenic mouse model [7]. However, IGFBP-2 binds IGF-2 with higher affinity than IGF-1. Furthermore, overexpression of IGFBP-2 is found in several malignancies including in transformed hair follicles of human BCC. IGFBP-2 might somehow be involved in epidermal progenitor cell expansion, invasion and angiogenesis [8]. IGFBP-4 has been shown to inhibit IGF-1- and IGF-2-mediated actions in vitro, and IGFBP-4 may be required for optimal action of IGF-2 in vivo rather than act as an inhibitor [7]. However, the precise roles of IGFBP-2 and -4 in hair biology are still unknown.

In addition, some hair loss treatments may exert their therapeutic effects via IGF-1. Theoretically, treatments that can stimulate the secretion of IGF-1 may slow hair loss. IGF-1 has also been shown to be upregulated in DP cells of patients with AGA who respond to finasteride [9]. It is possible that increased expression of IGF-1 mRNA in the DP cells of the 5 alpha reductase inhibitor responding patients may prolong anagen phase in balding areas. L-ascorbic acid 2-phosphate (Asc 2-P) promotes elongation of hair shafts and proliferation of ORS keratinocytes in vitro via the secretion of IGF-1 from DP cells through phosphatidylinositol 3-kinase. IGF-1 mRNA in DP cells upregulates, and IGF-1 protein in the conditioned medium of DP cells significantly increases after treatment with Asc 2-P [10].The similar effect is found in water soluble extract of Illicium anisatum; it is found to promote hair growth via induction of IGF-1, keratinocyte growth factor and vascular endothelial growth factor in the hair follicles [11].

IGF-1 itself might also be considered as new therapeutic options for the treatment for hair loss particularly androgenetic alopecia as well as alopecia areata. 3% liposomal IGF-1 in a liquid gel formulation is found to increase both hair growth and thickness in a hamster model. The safety profile is also studied. No evidence of hepatoxic and myelotoxic side effects has been found [12].

Lastly, hair-follicle-derived IGF-1, α-MSH and TGF- β1 are found to play part in active immune privilege restoration of the anagen hair bulb. IGF-1 together with α-MSH and TGF-β, which are proposed to be recruited whenever the hair follicle suffers from immune injury, can downregulate IFN-γ induced ectopic MHC class I expression in human anagen hair bulbs in vitro [13]. This phenomenon can be normalized by treatment with α-MSH, IGF-1 or TGF- β1 [14]. Therefore, IGF-1 is one of the promising candidates for the treatment of alopecia areata.

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