[Hormones and skin pigmentation: fundamentals and clinical relevance]

Skin pigmentation by the endogenous pigment melanin is a highly coordinated process in which hormones play a crucial role. They are synthesized not only in classical endocrine organs but also in the skin itself, which acts as an independent endocrine organ. Among the endocrine target structures of the skin, the melanocortin 1 receptor (MC1R) is of particular importance. Via its high expression and tonic activity in melanocytes, as well as by binding to natural melanocortins such as α‑melanocyte-stimulating hormone (α-MSH), being generated in the skin following ultraviolet (UV) light irradiation, MC1R crucially contributes to the different skin phototypes. Gene mutations of MC1R resulting in defective cyclic adenosine monophosphate (cAMP)-mediated signalling can lead to a shift of the eumelanin/pheomelanin ratio towards the pro-oxidant, yellowish-orange pheomelanin. In patients with Addison's disease and associated syndromes, ectopic proopiomelanocortin syndrome and primary adrenal cortex insufficiency elevated melanocortin levels result in increased melanin content of the skin. Two synthetic melanocortins, afamelanotide (NDP-α-MSH) and setmelanotide, are currently approved in Germany. By targeting MC1R directly (afamelanotide) or as a bystander effect (setmelanotide), both agents increase the skin melanin content. Non-licenced synthetic melanocortins, on the other hand, are used as lifestyle products in an unregulated manner. Additional hormones regulating melanogenesis and skin pigmentation include estrogens, thyroid hormones, insulin, insulin-like growth-factor‑1 and melatonin. They are of physiological and clinical relevance during pregnancy and in patients with melasma and vitiligo. Autoimmune thyroid disorders and diabetes are associated with non-segmental vitiligo. Melatonin appears to have a lightening effect on skin pigmentation by melanin.