Serotoninergic and melatoninergic systems are fully expressed in human skin

FASEB J. 2002 Jun;16(8):896-8. doi: 10.1096/fj.01-0952fje. Epub 2002 Apr 23.


We investigated the cutaneous expression of genes and enzymes responsible for the multistep conversion of tryptophan to serotonin and further to melatonin. Samples tested were human skin, normal and pathologic (basal cell carcinoma and melanoma), cultured normal epidermal and follicular melanocytes, melanoma cell lines, normal neonatal and adult epidermal and follicular keratinocytes, squamous cell carcinoma cells, and fibroblasts from dermis and follicular papilla. The majority of the samples showed simultaneous expression of the genes for tryptophan hydroxylase, arylalkylamine N-acetyltransferase (AANAT), and hydroxyindole-O-methyltransferase (HIOMT). The products of AANAT activity were identified by RP-HPLC with fluorimetric detection in human skin and in cultured normal and malignant melanocytes and immortalized keratinocytes; HIOMT activity was detected in human skin, keratinocytes, and melanoma cells. N-acetylserotonin (NAS) was detected by RP-HPLC in human skin extracts. NAS identity was confirmed further by LC/MS in keratinocytes. In conclusion, we provide evidence that the human skin expresses intrinsic serotonin and melatonin biosynthetic pathways.

MeSH terms

  • Acetylserotonin O-Methyltransferase / genetics
  • Acetylserotonin O-Methyltransferase / metabolism
  • Arylamine N-Acetyltransferase / genetics
  • Arylamine N-Acetyltransferase / metabolism
  • Cell Line
  • Gene Expression
  • Gene Expression Regulation, Enzymologic / radiation effects
  • Humans
  • Melanocytes / cytology
  • Melanocytes / enzymology
  • Melanoma / enzymology
  • Melanoma / pathology
  • Melatonin / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / analogs & derivatives*
  • Serotonin / metabolism*
  • Skin / metabolism*
  • Tryptophan Hydroxylase / genetics
  • Tryptophan Hydroxylase / metabolism
  • Tumor Cells, Cultured
  • Ultraviolet Rays


  • RNA, Messenger
  • Serotonin
  • Tryptophan Hydroxylase
  • Acetylserotonin O-Methyltransferase
  • Arylamine N-Acetyltransferase
  • Melatonin
  • N-acetylserotonin