CRH peptides modulate proliferation, melanogenesis and dendri-city in human follicular melanocytes
Abstract
Corticotropin-releasing hormone (CRH) is the most proximal element of the hypothalamic-pituitary-adrenal axis (HPA) and is the chief regulator of pituitary POMC gene expression and the subsequent production and secretion of POMC peptides. Previously, our laboratories documented cutaneous expression of CRH, urocortin and functional CRH receptors (CRH-Rs), suggesting their role in skin physiology and pathology. Human skin predominately expressed CRH-R1 with CRH-R2 being expressed primarily in the adnexal structures. While CRH-R activity has been implicated in the regulation of epidermal cell function, a role for these receptors in human hair biology has not yet been demonstrated. This study was designed to investigate the effects of modified CRH peptides (D-Glu20)-CRH, (D-Pro5)-CRH and (D-Pro4)-urocortin with respective selectivity for CRH-R1 and CRH-R2 on behaviour of cultured hair follicle melanocytes (HFMs) derived from scalp of seven normal individuals. HFMs were stimulated with these peptides (10−7−10−10 m) for 72 h. (D-Glu20)-CRH (10−8 m) and (D-Pro5)-CRH (10−9 and 10−10 m) markedly increased cell dendricity, melanogenesis and proliferation (P < 0.01) compared with unstimulated levels. While (D-Pro4)-urocortin failed to stimulate cell dendricity, this peptide did stimulate melanogenesis (10−8 m) (P < 0.01) and exhibited a biphasic proliferative response; stimulating pigment cell division at 10−7 and 10−8 m (P < 0.01) but inhibiting proliferation at 10−9 and 10−10 m (P < 0.01). Here, we demonstrate the existence of functionally active CRH-Rs in cultured human scalp HFM and show that signalling via these receptors modulates follicular melanocyte dendricity, melanogenesis and proliferation. Thus, activation of CRH-Rs may have a pivotal role in the regulation of follicular melanocyte homeostasis.
