On the Role of Melatonin in Skin Physiology and Pathology

Abstract

Melatonin has been experimentally implicated in skin functions such as hair growth cycling, fur pigmentation, and melanoma control, and melatonin receptors are expressed in several skin cells including normal and malignant keratinocytes, melanocytes, and fibroblasts. Melatonin is also able to suppress ultraviolet (UV)-induced damage to skin cells and shows strong antioxidant activity in UV exposed cells. Moreover, we recently uncovered expression in the skin of the biochemical machinery involved in the sequential transformation of L-tryptophan to serotonin and melatonin. Existence of the biosynthetic pathway was confirmed by detection of the corresponding genes and proteins with actual demonstration of enzymatic activities for tryptophan hydroxylase, serotonin Nacetyl-transferase, and hydroxyindole-O-methyltransferase in extracts from skin and skin cells. Initial evidence for in vivo synthesis of melatonin and its metabolism was obtained in hamster skin organ culture and in one melanoma line. Therefore, we propose that melatonin (synthesized locally or delivered topically) could counteract or buffer external (environmental) or internal stresses to preserve the biological integrity of the organ and to maintain its homeostasis. Furthermore, melatonin could have a role in protection against solar radiation or even in the management of skin diseases.

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

“…Increasing evidence in the field suggests that melatonin acts at many extrapineal sites such as the gastrointestinal tract (11,12), the blood cell system (13), the retina (14), the bone marrow (15,16) and the skin (17)(18)(19)(20)(21)(22). In the epidermal keratinocytes, a constitutive and UV-induced melatonin metabolism has recently been described (23).…”

“…Under physiologic conditions, melatonin participates in the regulation of keratinocyte proliferation (24)(25)(26), hair growth (26)(27)(28)(29)(30)(31) and melanogenesis (32,33). In conditions of oxidative stress, it acts as an antioxidant (18,(34)(35)(36) and UV-protective substance (18,22,37,38). These actions may result in protective, proliferative and antiapoptotic effects to ensure the survival of non-neoplastic cells.…”

“…Cytosolic NRH:quinone oxidoreductase 2 (NQO2, QR2) possesses melatonin binding sites previously described as MT3 receptor (57), differing in this aspect from NAD(P)H:quinone oxidoreductase 1 (NQO1, QR1) (58). Melatonin nuclear receptors, recently identified in keratinocytes, melanocytes and fibroblasts (18) as well as in hair follicles (28), belong to the retinoid orphan receptor subfamily (RZR/ROR). It was shown that all these human (18,40,59).…”

“…Melatonin nuclear receptors, recently identified in keratinocytes, melanocytes and fibroblasts (18) as well as in hair follicles (28), belong to the retinoid orphan receptor subfamily (RZR/ROR). It was shown that all these human (18,40,59). Here, we tested melatonin for its potential oncostatic effects by assaying for proliferation and colony growth suppression in four different melanoma cell lines (three amelanotic lines including SBCE2, WM-98 and WM-164 derived from vertical and radial growth phases or metastasis, respectively, and SKMEL-188, which can produce melanin pigment).…”

Age-related changes in melatonin synthesis in rat extrapineal tissues

“…This presence does not necessarily indicate an endogenous synthesis because the high lipophilic nature permits its transfer. To date, extrapineal melatonin synthesis has been demonstrated only in retina, harderian gland, brain, gut, ovary, testes, inner ear and immune system including bone marrow, lymphocytes, macrophages and, more recently, in thymus (Kvetnoy, 1999;Bubenik, 2002;Carrillo-Vico et al, 2004;Slominski et al, 2005). In general, while pineal melatonin seems to act as a typical hormone reaching target cells through the bloodstream, extrapineal melatonin may play a key role as an intra-, auto-and paracrine signal molecule in those tissues where it is synthesized (Carrillo-Vico et al, 2004).…”