New frontiers in human hair follicle (neuro‐)endocrinology

Recently, we have shown that normal human scalp hair follicles in anagen VI (a) synthesize CRH, ACTH, alpha‐MSH and cortisol and display a fully functional equivalent of the hypothalamus–pituitary–adrenal axis (Ito et al. FASEB J 2005) (b) synthesize melatonin, up‐regulate melatonin synthesis and secretion upon stimulation with noradrenaline (just like in the pineal gland), and express melatonin receptors in a hair cycle‐dependent manner (Kobayashi et al. FASEB J 2005) and (c) synthesize prolactin, express functional prolactin receptors, and respond to their stimulation by premature catagen induction, which is mediated in part via up‐regulation of TGFβ2 (Foitzik et al. Am J Pathol, in press). Besides these, by now established, aspects of hair follicle (neuro‐) endocrinology, we present preliminary evidence that points to exciting new frontiers in this field: for example, human anagen VI scalp hair follicles also express erythropoietin and its receptor (EPO and EPO‐R) on the gene and protein level and up‐regulate EPO‐R expression under conditions of hypoxia, and that these hair follicles may have established yet another hypothalamus–pituitary axis equivalent, the TRH‐TSH system. Studying the effects of calcitonin gene‐related peptide (CGRP), a key skin neuropeptide associated, e.g., with stress responses and neurogenic inflammation, on organ‐cultured human hair follicles, we also noted that CGRP inhibits both hair matrix keratinocyte proliferation in situ and hair follicle pigmentation. After defining the most immediately pressing open questions that remain to be addressed in these areas, our own data are discussed in the context of how the organ‐culture of human scalp hair follicles can be exploited for addressing questions of general importance in human dermatoendocrinology.