Characterization of serotonin and N‐acetylserotonin systems in the human epidermis and skin cells

Abstract

Tryptophan hydroxylase (TPH) activity was detected in cultured epidermal melanocytes and dermal fibroblasts with respective Km of 5.08 and 2.83 mM and Vmax of 80.5 and 108.0 µmol/min. Low but detectable TPH activity was also seen in cultured epidermal keratinocytes. Serotonin and/or its metabolite and precursor to melatonin, N-acetylserotonin (NAS), were identified by LC/MS in human epidermis and serum. Endogenous epidermal levels were 113.18 ± 13.34 and 43.41 ± 12.45 ng/ mg protein for serotonin (n = 8/8) and NAS (n = 10/13), respectively. Their production was independent of race, gender, and age. NAS was also detected in human serum (n = 13/13) at a concentration 2.44 ± 0.45 ng/mL, while corresponding serotonin levels were 295.33 ± 17.17 ng/mL (n = 13/13). While there were no differences in serum serotonin levels, serum NAS levels were slightly higher in females.Immunocytochemistry studies showed localization of serotonin to epidermal and follicular keratinocytes, eccrine glands, mast cells, and dermal fibrocytes. Endogenous production of serotonin in cultured melanocytes, keratinocytes, and dermal fibroblasts was modulated by UVB. In conclusion, serotonin and NAS are produced

Reconsidering the Role of Melatonin in Rheumatoid Arthritis

“…In the skin, melatonin can regulate cutaneous pigmentation and perform photoprotective and anticancer activities [10,11]. N-acetylserotonin, a precursor to melatonin, enters the systemic circulation from different peripheral organs for transformation to melatonin [12]. Furthermore, the effects of melatonin can be mediated by its metabolites because of the rapid metabolism of melatonin at the peripheral sites [13,14].…”

Current and emerging treatments targeting the neuroendocrine system for disorders of the skin and its appendages

“…The skin has its own serotonergic system. [211][212][213] Thus, targeting components of the serotonergic system has a high potential for the treatment of different inflammatory skin diseases [214][215][216] and could promote wound healing [217] and hair pigmentation, [218,219] as several studies indicate.…”

Bases for Treating Skin Aging With Artificial Mitochondrial Transfer/Transplant (AMT/T)

“…Melatonin is a hormone product of the pineal gland that regulates the circadian rhythm. It has been observed that melatonin can be produced by epidermal and hair follicle keratinocytes ( Kleszczynski and Fischer, 2012 ; Slominski et al, 2020 , 2008 ). Melatonin has ROS scavenging properties it promotes antioxidant and DNA repair mechanisms, inducing immune modulation and antitumor properties ( Slominski et al, 2018a ).…”

“…This improves the mitochondrial membrane potential by inhibiting the activation of the permeability pore, stimulating the activity of uncoupling proteins (UCPs), and inducing an increase in ATP production ( Slominski et al, 2018a ). Melatonin and its derivatives N1-acetyl-N2 -formyl-5-methoxykynurenine (AFMK) and N-acetyl serotonin (NAS) are expressed in the human skin and have shown antioxidant and antiapoptotic activity ( Skobowiat et al, 2018 ; Slominski et al, 2020 ). The secretion of melatonin by the pineal gland declines with age ( Hardeland, 2012 ) and possibly affects the presence and production of melatonin in the skin.…”