Thyroid hormones directly alter human hair follicle functions: Anagen prolongation and stimulation of both hair matrix keratinocyte proliferation and hair pigmentation

Context: Both insufficient and excess levels of thyroid hormones (T ₃ and T₄) can result in altered hair/skin structureandfunction (e.g. effluvium). However, it is still unclear whether T₃ and T₄ exert any direct effects on human hair follicles (HFs), and if so, how exactly human HFs respond to T₃/T₄ stimulation. Objective: Our objective was to asses the impact of T ₃/T₄ on human HF in vitro. Methods: Human anagen HFs were isolated from skin obtained from females undergoing facelift surgery. HFs from euthyroid females between 40 and 69 yr (average, 56 yr) were cultured and treated with T₃/T₄. Results: Studying microdissected, organ-cultured normal human scalp HFs, we show here that T₄ up-regulates the proliferation of hair matrix keratinocytes, whereas their apoptosis is down-regulated by T₃ and T₄. T₄ also prolongs the duration of the hair growth phase (anagen) in vitro, possibly due to the down-regulation of TGF-β2, the key anagen-inhibitory growth factor. Because we show here that human HFs transcribe deiodinase genes (D2 and D3), they may be capable of converting T₄ to T₃. Intrafollicular immunoreactivity for the recognized thyroid hormone-responsive keratins cytokeratin (CK) 6 and CK14 is significantly modulated by T₃ and T₄ (CK₆ is enhanced, CK14 down-regulated). Both T₃ and T₄ also significantly stimulate intrafollicular melanin synthesis. Conclusions: Thus, we present the first evidence that human HFs are direct targets of thyroid hormones and demonstrate that T₃ and/or T₄ modulate multiple hair biology parameters, ranging from HF cycling to pigmentation.