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 T-4) can result in altered hair/skin structure and function (e. g. effluvium). However, it is still unclear whether T-3 and T-4 exert any direct effects on human hair follicles (HFs), and if so, how exactly human HFs respond to T-3/T-4 stimulation. Objective: Our objective was to asses the impact of T-3/T-4 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 T-3/T-4. Results: Studying microdissected, organ-cultured normal human scalp HFs, we show here that T-4 up-regulates the proliferation of hair matrix keratinocytes, whereas their apoptosis is down-regulated by T-3 and T-4. T-4 also prolongs the duration of the hair growth phase (anagen) in vitro, possibly due to the down-regulation of TGF-beta 2, 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 T-4 to T-3. Intrafollicular immunoreactivity for the recognized thyroid hormone-responsive keratins cytokeratin (CK) 6 and CK14 is significantly modulated by T-3 and T-4 (CK6 is enhanced, CK14 down-regulated). Both T-3 and T-4 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 T-3 and/or T-4 modulate multiple hair biology parameters, ranging from HF cycling to pigmentation. (J Clin Endocrinol Metab 93: 4381-4388, 2008)