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  • Showing results for hardman et al. 2015, plos one 10 e0121878. Your search for Hardmann et al. 2015, PLoS One 10:e0121878 retrieved no results.
PLoS One. 2015 Mar 30;10(3):e0121878. doi: 10.1371/journal.pone.0121878. eCollection 2015.

Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle.

Author information

1
The Dermatology Centre, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom; Doctoral Training Centre in Integrative Systems Biology, Manchester Interdisciplinary Bio centre, University of Manchester, Manchester, United Kingdom.
2
The Dermatology Centre, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom.
3
The Farjo Hair Institute, Manchester, United Kingdom.
4
The Dermatology Centre, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom; Department of Dermatology, University of Muenster, Muenster, Germany.

Abstract

The human hair follicle (HF) exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1) prolonging active hair growth (anagen) and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4) also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM) treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2) were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease.

PMID:
25822259
PMCID:
PMC4379003
DOI:
10.1371/journal.pone.0121878
[Indexed for MEDLINE]
Free PMC Article

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