Corticotropin releasing hormone (CRH), melanocortins (MC) and thyrotropin releasing hormone (TRH) stimulate pigmentation and melanocyte function in the human hair follicle

Abstract

Melanocortins (MC) such as adrenocorticotropic hormon (ACTH) and α‐melanocyte‐stimulating hormone (αMSH) are neuropeptides derived from the prohormone proopiomelanocortin (POMC). It is now well established that the human skin is not only a target but also a local source for MCs. Almost all cutaneous cell types express MCs and MC‐receptor (MCRs) in vitro. The POMC peptides, their receptors and CRH the main inducer of POMC gene/protein expression in the pituitary and in skin ‐were also detected in human scalp hair follicles (HFs). MCs regulate pigmentation: stimulate melanogenesis, dendricity and proliferation in epidermal melanocytes, and similar effect was reported recently on cultured melanocytes derived from the outer root sheath of human HFs. TRH is the most proximal member of the hypothalamic‐pituitary‐thyroid (HPT) axis. In amphibian skin, TRH also regulates POMC release, which leads to skin darkening via αMSH‐MC1R interactions. Recently we found TRH and TRH‐R expression in human HFs. Therefore, we examined the – as yet ill‐explored – effect of exogenous CRH, ACTH, αMSH and TRH on melanin production, melanocytes number and dendricity in normal, microdissected, organ‐cultured human anagen scalp HFs. Melanin production was measured by quantitaive Masson‐Fontana histochemistry, and melanocyte dendricity were assessed by immunohistochemistry against the melanosome marker gp100 (Nki‐beteb). The melanin content increased significantly after αMSH (10–100 nM) and TRH(1–10 ng/ml) addition to the medium. Total Nki‐beteb immunoreactivity was significantly elevated in the HF melanocytes treated with αMSH, thus confirming the Masson‐Fontana results. TRH, CRH (10 nM–100 pM) and MC (10–100 nM) also stimulated dendrite formation of HF pigmentary unit melanocytes. CRH, MCs and TRH as well were able to compensate the significant decline of the melanin content caused by catagen induction with TGFβ2. This provides unequivocal evidence that CRH, ACTH and a‐MSH stimulate normal human hair follicle pigmentation in situ. We also show for first time that TRH, a key regulator of pigmentation in amphibian skin, might play similar role in human HF.