F6 CIRCADIAN CLOCK GENES ARE EXPRESSED IN HUMAN HAIR FOLLICLES

Akram M., Müller-Röver S., Bull J., Chronnell C., McKay I., Philpott M., Centre for Cutaneous Research. St Bartholomew’s and the Royal London School of Medicine and Dentistry, QMW College London E1 2AT.

The molecular controls of hair follicle cycling are unknown. However, it is possible that the hair growth cycle may be under the control of a ‘hair cycle clock’. Self-sustaining, endogenous, oscillators or circadian clocks drive many biological activities. It is known that circadian sleep-wake cycles depend on photoreceptors in the retina relaying signals to the suprachiasmatic nucleus (SCN) in the brain. Here photoperiodicity is established through a complex feedback loop involving the auto-regulated expression of a class of PAS (PER-ARNT-SIM) domain transcription factors including Clock,  BMAL1 and the three per (period) genes. Recently it has been demonstrated that these genes are under circadian control in multiple rat somatic tissues including heart, lung, spleen, liver and kidney. These may therefore, be candidates for the ‘hair cycle clock’. To investigate this we have studied human Clock expression in human skin and hair follicles using RT-PCR and in situ hybridisation (ISH). We have found that human clock gene is expressed in human scalp skin as well as in cultured, human, keratinocytes and dermal papilla (DP) fibroblasts. ISH carried out using a digoxigenin labelled probe to human clock showed expression in both the interfollicular epidermis as well as in all epithelial compartments of the hair follicle. The PAS domain proteins are a large family of transcription factors that form heterodimers which bind to the promoter region of a wide range of target genes. Interactions between PAS domain proteins and basic helix-loop-helix (bHLH) proteins may regulate the genes that control hair follicle cycling.