Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation

Abstract

Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.

Differential expression of HPA axis homolog in the skin

“…The skin is continuously exposed to many hostile environmental factors (chemical and biological) and to acute transfers of solar, thermal or mechanical energy (Slominski and Pawelek, 1998;Slominski and Wortsman, 2000;Slominski et al, 2000d). In part as a mechanism of defense, skin cells produce hormones, neurotransmitters and neuropeptides and express cognate functional receptors Slominski et al, 2004b;Slominski and Wortsman, 2000;Slominski et al, 2000d). Besides being produced locally in epidermal, adnexal and dermal cells, hormones and neurotransmitters are also released in situ from cutaneous nerve endings (Slominski and Wortsman, 2000).…”

“…These profound neuroendocrine activities of skin complement its exocrine activities, performed by the adnexal structures e.g., eccrine, apocrine and sebaceous glands and hair follicles (Slominski and Wortsman, 2000;Stenn and Paus, 2001;Zouboulis and Bohm, 2004). Exocrine activities function to strengthen the epidermal barrier and control thermoregulation, or participate in the defense against microorganisms, or in social communication (Slominski, 2005;Slominski et al, 2004b;Slominski and Wortsman, 2000;Stenn and Paus, 2001;Zouboulis and Bohm, 2004).…”

“…Such mechanisms are represented by the barrier forming properties of the epidermis, the secretory and protective activities of adnexal structures, skin immune and pigmentary systems as well as by vascular and mesenchymal components of the dermis Luger et al, 1999;Slominski, 2005;Slominski et al, 2004b;Slominski and Wortsman, 2000;Stenn and Paus, 2001;Zouboulis and Bohm, 2004). It is these mechanisms, as well as the precise coordination of their responses, that appear to be functionally served by local cutaneous neuroendocrine activities (Slominski, 2005;Slominski and Wortsman, 2000;Slominski et al, 2000d).…”

α‐melanocyte–stimulating hormone suppresses bleomycin‐induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: Melanocortin peptides as a novel treatment strategy for scleroderma?

“…Alpha-melanocyte-stimulating hormone is derived from pro-opiomelanocortin (POMC), both of which are produced by the skin itself (11). In addition to its pigmentary action (12), ␣-MSH has many other effects, such as immunomodulation and regulation of exocrine activity and apoptosis (13)(14)(15). With regard to HDFs, we found that ␣-MSH suppresses TGF␤1-induced collagen synthesis in HDFs in vitro.…”

Involvement of Nurr-1/Nur77 in corticotropin-releasing factor/urocortin1-induced tyrosinase-related protein 1 gene transcription in human melanoma HMV-II cells

“…Melanocytes are a type of sensory and regulatory cell with neuroendocrine activity (Tsatmali et al, 2002), producing stress-related neurotransmitters and neuropeptides in response to various endogenous and exogenous factors derived from neighboring keratinocytes (Slominski, 2009;Slominski and Wortsman, 2000). Cutaneous melanin pigmentation occurs in response to external and internal stresses (Slominski et al, 2000a;Slominski et al, 2004b;Ito et al, 2005).…”