Is thyrotropin-releasing hormone a novel neuroendocrine modulator of keratin expression in human skin?

BACKGROUND: Hair and epithelial keratins constitute the major structural components of the skin and its appendages, including the hair fiber. While selected steroid hormones are appreciated to regulate specific keratins, little is known about the neuroendocrine control of human hair keratin expression. Preliminary evidence had suggested that thyrotropin-releasing hormone (TRH) may regulate keratin gene transcription. OBJECTIVE: We wanted to clarify whether TRH operates as a novel neuroendocrine regulator of human hair and epithelial keratin expression under physiologically relevant conditions in situ. METHODS: Microdissected human female scalp hair follicles (HFs) and female scalp skin were treated in serum-free organ culture for 12h - 6d with 100ng/ml TRH or vehicle. Both quantitative immunohistomorphometry and RT-qPCR were utilized to assess expression of selected keratins. RESULTS: TRH significantly increased expression of the hair keratins K31 and K32, while that of K85 and K86, and of the epithelial keratins K14 and K17 was reduced. In the interfollicular epidermis, TRH stimulated expression of K6, K14 and K17, both at the mRNA and protein levels. Stimulation of the same keratins was also evident in the eccrine sweat and sebaceous glands. CONCLUSIONS: Selected human hair and epithelial keratins are modulated in situ. This may be relevant to explain hair shaft growth-promoting effects of TRH. Our pilot study suggests that the neuroendocrine controls that regulate the expression of human keratins deserve more systematic exploration and that these may be harnessed therapeutically.