Thyroxine Differentially Modulates the Peripheral Clock: Lessons from the Human Hair Follicle

The study investigated the effects of thyroxine (T4) on the peripheral clock activity in human hair follicles (HFs). It was found that T4 treatment significantly reduced the protein and transcript levels of clock genes BMAL1 and PER1 over 24 hours, although their rhythmicity was maintained. After 6 days, T4 up-regulated the transcript and/or protein levels of all core clock genes, including in the HF bulge, which contains epithelial stem cells. This suggested that T4 modulated the peripheral molecular clock, indicating that thyroid dysfunction could lead to a disordered peripheral clock. The findings raised the possibility that short-term, pulsatile T4 treatment might be used to modulate circadian activity in peripheral tissues to treat clock-related diseases.