Expression and regulation of pro‐opiomelanocortin‐derived peptides in human hair growth and pigmentation

Human skin provides for the local cleavage of pro‐opiomelanocortin (POMC) to yield multiple peptide products, e.g. α‐MSH, ACTH and β‐endorphin (β‐end). α‐MSH and ACTH are well documented to regulate human skin pigmentation. We have recently shown that human epidermal melanocytes express a fully functioning β‐end/µ‐opiate receptor system, and that β‐end has potent melanogenic, mitogenic and dendritogenic effects in cultured epidermal melanocytes. However, little is known about their role in human hair follicle (HF) biology. We have characterized the expression and regulation of β‐end, ACTH, α‐MSH and their receptors in human haired scalp and in cultured HF melanocytes, keratinocytes and fibroblasts by immunochemistry, detection of mRNA transcripts and by assessment of potential melanogenic, dendritogenic and mitogenic effects of these peptides in vitro . These studies show that the POMC peptide system is expressed in HF cells as a function of their anatomic location and differentiation status during the hair growth cycle. All three peptides exhibit similar melanogenic, mitogenic and dendritogenic effects in cultured HF melanocytes. Moreover, while the in situ expression profiles of ACTH and α‐MSH are similar, they differ strikingly from β‐end for all follicular cell populations. One such example is the persistent expression of the former in the hair inductive follicular papilla (FP) throughout the entire hair cycle (but are expressed variably in HF keratinocytes and melanocytes). However, β‐end expression is low to undetectable in the FP during hair growth. In toto , these results indicate that POMC peptides are involved in regulating human HF growth and pigmentation and that alterations in POMC homeostasis may be contribute to pathology.