Thyroxine differentially modulates the peripheral clock: Lessons from the human hair follicle

Jonathan A. Hardman, Iain S. Haslam, Nilofer Farjo, Bessam Farjo, Ralf Paus

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

LanguageEnglish
Article numbere0121878
Number of pages15
JournalPLoS One
Volume10
Issue number3
DOIs
Publication statusPublished - 30 Mar 2015
Externally publishedYes

Fingerprint

hair follicles
Hair Follicle
L-thyroxine
thyroxine
Thyroxine
Clocks
Periodicity
Pigmentation
ARNTL Transcription Factors
Gene Knockdown Techniques
Circadian Clocks
Cyclin D1
pigmentation
Thyroid Hormones
Human Activities
Hair
Genes
Cell Cycle
Thyroid Gland
Stem Cells

Cite this

Hardman, Jonathan A. ; Haslam, Iain S. ; Farjo, Nilofer ; Farjo, Bessam ; Paus, Ralf. / Thyroxine differentially modulates the peripheral clock : Lessons from the human hair follicle. In: PLoS One. 2015 ; Vol. 10, No. 3.
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Thyroxine differentially modulates the peripheral clock : Lessons from the human hair follicle. / Hardman, Jonathan A.; Haslam, Iain S.; Farjo, Nilofer; Farjo, Bessam; Paus, Ralf.

In: PLoS One, Vol. 10, No. 3, e0121878, 30.03.2015.

Research output: Contribution to journalArticle

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