In Vitro Main Pathways of Steroid Action in Cultured Hair Follicle Cells: Vascular Approach

Abstract

The known role of steroids on the hair follicle leads us to investigate their effects on hair follicle cell angiogenic responses in vitro. We verified, using the immunohistochemical technique, whether human occipital scalp follicle cells express steroid receptors in vitro. We showed that androgen and estrogen receptors were expressed by dermal papilla cells (DPC) and keratinocytes from the outer root sheath in vitro. With regard to steroidal enzymes (type I and II 5alpha-reductases and Cytochrome-p-450-aromatase), the type I 5alpha-reductase gene is much more expressed in DPC than in dermal fibroblasts; however, the type II 5a-reductase gene is transcribed more in dermal fibroblasts than in DPC. The transcription of the two 5alpha-reductase isoform genes in cultured DPC is regulated by a 5alpha-reductase inhibitor. We also demonstrated that DPC, dermal fibroblasts, and outer root shealth keratinocytes expressed cytochrome-p-450-aromatase. Using ELISA and reverse transcriptase-polymerase chain reaction, we investigated the role played by some steroids (estrogens, androgens, antiandrogens) in the modulation of vascular endothelial growth factor (VEGF) expression by DPC. The association of different treatments of DPC (5alpha-reductase inhibitor and androgen receptor antagonist) shows a great stimulation of VEGF and aromatase expression. Strong stimulation of VEGF protein and gene expression is observed in the presence of 17beta-estradiol. Also, the concentration-dependent inhibition of VEGF expression by DPC using the cytochrome-p-450-aromatase inhibitor, confirms the involvement of this estrogenic pathway in the regulation of VEGF expression in vitro.

Enhanced VEGF Expression in Hair Follicle Dermal Papilla Cells by Centella asiatica Linn.

“…β-catenin causes the signaling of human follicle dermal papilla cell proliferation (Driskell et al, 2011). The β-catenin activity in the human follicle dermal papilla cells regulates a number of other signaling pathways, including the phosphorelation of downstream signalling, such as the VEGF pathway, that stimulates cell proliferation (Lachgar et al, 1999;Driskell et al, 2011). VEGF also plays an important role in angiogenesis in follicle dermal papilla cells (Yano et al, 2001).…”

Perifollicular Fibrosis: Pathogenetic Role in Androgenetic Alopecia

“…Compared to T, DHT has approximately five fold greater affinity for the AR and DHT binding to AR in hair follicles is commonly accepted as the first step leading to the miniaturizing of follicles seen in AGA. [11][12][13] The other is higher levels of AR in cells from balding scalp hair follicles with similar properties to those from non-balding scalp.…”

“…11) Finasteride is well known as a potent and highly selective 5a-R type-II inhibitor. 12,13) It is reasonable that the action mechanisms of finasteride on AGA can be explained as inhibition of collagen synthesis in the follicular DFs, which lessens perifollicular fibrosis and formation of angiofibrotic tract involved in catagen induction.…”

Differential expression of steroid 5α-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer

“…Finasteride has been shown to stimulate VEGF expression in other cells as well, e.g. dermal papilla cells, which are targets for many circulating hormonal and growth factors (Lachgar et al 1999). Dutasteride, another inhibitor of 5a-reductase, blocks the activity of both isozymes, and is currently being investigated for both PC risk reduction and treatment (Rittmaster et al 2009).…”