The hair follicle dermal papilla which controls hair growth, is characterized in the anagen phase by a highly developed vascular network. We have demonstrated in a previous study that the expression of an angiogenic growth factor called vascular endothelial growth factor (VEGF) mRNA varied during the hair cycle. VEGF mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase, but during the catagen and telogen phases. VEGF mRNA is less strongly expressed. This involvement of VEGF during the hair cycle allowed us to determine whether VEGF mRNA expression by DPC was regulated by minoxidil. In addition, the effect of minoxidil on VEGF protein synthesis in both cell extracts and DPC-conditioned medium, was investigated immunoenzymatically. Both VEGF mRNA and protein were significantly elevated in treated DPC compared with controls. DPC incubated with increasing minoxidil concentrations (0.2, 2, 6, 12 and 24 mumol/L) induced a dose-dependent expression of VEGF mRNA. Quantification of transcripts showed that DPC stimulated with 24 mumol/L minoxidil express six times more VEGF mRNA than controls. Similarly, VEGF protein production increases in cell extracts and conditioned media following minoxidil stimulation. These studies strongly support the likely involvement of minoxidil in the development of dermal papilla vascularization via a stimulation of VEGF expression, and support the hypothesis that minoxidil has a physiological role in maintaining a good vascularization of hair follicles in androgenetic alopecia.

The transition of the late anagen to the catagen phase is concomitant with the disappearance of perifollicular capillaries, and therefore cyclical hair growth might depend on the ability of the dermal papilla to synthesize and release soluble growth and differentiation factors toward pre-existing capillaries. We characterized an angiogenic growth factor in the conditioned medium of dermal papilla cells indistinguishable from vascular endothelial growth factor as judged by biochemical and immunologic criteria. In addition, these cells bind vascular endothelial, growth factor on two binding sites and proliferate or migrate in the presence of this growth factor. Moreover, neutralizing antibodies inhibit these biologic effects, confirming that vascular endothelial growth factor might contribute to hair growth either by acting directly on papilla cells or by stimulating the local vascularization.

Background: Vascular endothelial growth factor (VEGF), a potent angiogenic factor and vasodilator, is strongly expressed by epidermal keratinocytes in many angiogenesis-dependent skin disorders. Retinoids may modulate VEGF in skin and this may be related to an effect on rosacea. Aim: To investigate the effect of retinaldehyde on VEGF production by human keratinocytes. Methods: The effects of different concentrations of retinoids (all-trans-retinal and all-trans-retinoic acid) on VEGF production by cultured human skin keratinocytes in both cell extracts and supernatants were determined. Expression of VEGF was analyzed by enzyme-linked immunosorbent assay (ELISA) and RT-PCR. Results: The amount of cell-associated and secreted VEGF strongly decreased with retinoid concentration (e.g. 48, 69% inhibition at 0.1 µM all-trans-retinal and -retinoic acid, respectively, in the supernatants). In parallel, approximately 25% inhibition of VEGF mRNA expression was obtained in the presence of 0.01 µM all-trans-retinal. Conclusion: The decrease in VEGF expression by keratinocytes on contact with retinoids may prevent skin neoangiogenesis in certain skin diseases.

Dermal papilla cells of rat vibrissa follicles cultivated in monolayers and in three-dimensional collagen gels show a different morphology in these culture systems. Dermal papilla cells cultured in lattices tend to express morphological features resembling those seen in vivo. Quantification of total collagen by incorporation of 3H-proline in monolayer cultures and in collagen lattices show that the amount of collagen found in dermal papilla cells is higher than that secreted. Moreover, collagen synthesis measured in lattices is reduced to about 50% of that found in monolayer cultures. The influence of growth factors on collagen synthesis by hair dermal papilla cells was investigated. We studied the effects of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and minoxidil on collagen synthesis in monolayers and in lattices. VEGF, bFGF and minoxidil significantly decreased the total amount of collagen. In monolayer cultures, there was approximately a 30% inhibition of collagen production with 5 ng/ml bFGF, 0.1 ng/ml VEGF and 100 ng/ml minoxidil. However, in the lattices this inhibition was reduced to about half. These results suggest that both culture substrate and growth factors influence collagen production by rat hair dermal papilla cells.

Summary We report two brothers afflicted with extreme sebaceous hyperplasia of the face and the neck, with considerable sebaceous hyperplasia, but no acne. Biopsy confirmed a simple isolated sebaceous hyperplasia. This familial dermatosis has apparently not been described previously.