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. 2014 Feb 20;71(16):2997–3025. doi: 10.1007/s00018-014-1579-2

Table 1.

Evidences of extrapineal melatonin synthesis in mammals

Tissue Species Experimental condition Enzyme expression Melatonin detection Melatonin levels Enzyme activity Precursors used Metabolites measured References
Brain Rat Tissue homogenate, sham-PX, Px mRNA, DNA: AANAT, ASMT HPLC 2,000–5,000 pg/mg prot (a) AANAT, ASMT

[14C]AC

[14C]SAM

[14C]Ac-Trp

[14C]melatonin

 [77]
Brain, liver Rat Subcellular SPx, Px n.a. HPLC-FD 5–300 pg/mg prot n.a. n.a. n.a. [15]
ARPE-19 cells Human Cell culture mRNA: TPH1, TPH2, AANAT, ASMT protein: TH1, AANAT HPLC-FD (b) n.a. n.a. n.a. [134]
Retina Rat Tissue homogenate n.a. n.a. n.a. AANAT [14C]AC Ac-Trp [129]
Retina Monkey Tissue homogenate mRNA, protein: AANAT, ASMT RIA n.a. AANAT, ASMT

[3H]AC

[3H]SAM

[3H]Ac-Trp

[3H]melatonin

 [41]
Retina Golden hamster Culture n.a. RIA 20–55 pg/ml (c) n.a. n.a. n.a. [130]
Y79 retinoblastoma cells Human Culture mRNA, DNA: AANAT, ASMT n.a. n.a. n.a. n.a. n.a. [133]
Lens Rabbit Tissue homogenate n.a. RIA 35–58 pg/lens AANAT

AC

SAM

Ac-Trp

Melatonin

 [145]
Lens Rat Tissue homogenate mRNA, protein: AANAT, ASMT n.a. n.a. n.a. n.a. n.a. [146]
Bone marrow Rat Tissue homogenate, Px n.a. RIA, ICC 750 pg/mg prot AANAT, ASMT

[14C]AC

[14C]SAM

[14C]Ac-Trp

[14C]-melatonin

 [158]
PBMN Human Cell culture, tissue mRNA, DNA: AANAT, ASMT HPLC-FD 400–600 pg/ml (d) AANAT, ASMT

AC, Trp

SAM

Ac-Trp

Melatonin

 [150]
Thymus Rat Tissue homogenate, SPx, Px mRNA, DNA: AANAT, ASMT HPLC-FD 0–9,500 pg/mg prot (e) AANAT, ASMT

AC, Trp

SAM

Ac-Trp

melatonin

 [152]
Thymus spleen Rat Tissue homogenate mRNA, DNA: AANAT, ASMT ELISA 1–40,000 pg/mg prot AANAT, ASMT

[14C]AC

[14C]SAM

[14C]Ac-Trp

[14C]melatonin

 [14]
RBL-2H3 mast cells Rat In vitro culture n.a. ELISA 6–15 pg/ml (f) AANAT, ASMT

[14C]AC

[14C]SAM

[14C]Ac-Trp

[14C]melatonin

 [161]
SKMEL188 human melanoma cells Human, roe Cell culture mRNA: TPH, ASMT LC/MS (g) TPH, AANAT, ASMT

[3H]TP

AC, Trp, SAM

[3H]HTP

NAS

Ac-Trp,

melatonin

 [164]
Skin Hamster Cell culture n.a. HPLC, GC/MS n.a. n.a. [3H]HT

[3H]NAS

[3H]melatonin

[3H]5MT

NAS

 [163]
Ovary Rat, human Tissue homogenate n.a. HPLC-FD, RIA 139–348 pg/mg prot AANAT, ASMT

AC, Trp

SAM, NAS

Ac-Trp

Melatonin

 [250, 252]
Placenta Human Cell culture, villous trophoblast mRNA: AANAT, ASMT n.a. n.a. AANAT, ASMT

[14C]AC

[14C]SAM

[14C]Ac-Trp

[14C]melatonin

 [266]
Liver, kidney, heart Rat Tissue homogenate mRNA, DNA:AANAT, ASMT ELISA 900–2,500 pg/mg prot AANAT, ASMT [14C]AC [14C]SAM

[14C]Ac-Trp

[14C]melatonin

 [14]
Thymus, spleen, platelets, lung, heart, kidney, muscle, liver, stomach fundus, gut, testis, spinal cord, brain Rat Tissue homogenate mRNA: AANAT, ASMT n.a. n.a. n.a. n.a. n.a. [4]

References include only those related to the original report of melatonin synthesis in a given tissue/organ; more information in the text

(a), day/night difference at 60 days after birth; (b), undetectable in untreated cells, evidenced after incubation with 100 μM tryptophan; (c), melatonin released from the cultured retinas; (d), melatonin content in peripheral blood mononuclear cells after 24–72 h of incubation; (e), maximum day/night levels at 7 days after birth; (f), melatonin released to the incubation medium; (g) melatonin levels not indicated; n.a., not assayed; 5MT, 5-methoxytryptamine; AANAT, aralkylamine N-acetyltransferase; AC, acetyl coenzyme A; Ac-Trp, N-acetyltryptamine; ASMT, acetylserotonin O-methyltransferase; [14C]AC, [14C]-acetyl-coenzyme A; [14C]Ac-Trp, [14C]N-acetyl tryptamine; [14C]SAM, S-[methyl-14C]adenosyl-l-methionine; ELISA, enzyme-linked immunosorbent assay; GC/MS, gas chromatographic/mass spectroscopy; [3H]HTP, [3H]5-hydroxy tryptophan; [3H]TP, [3H]tryptophan; HPLC, high performance liquid chromatography; HPLC-FD, HPLC with fluorometric detection; HT, serotonin; ICC, immunocytochemistry; LC/MS, liquid chromatography-mass spectrometry; NAS, N-acetyl serotonin; PBMN, human peripheral blood mononuclear cells; Px, pinealectomy; RIA, radioimmunoassay; SAM, S-adenosyl-l-methionine; SPx, sham pinealectomy; TPH1 and TPH2, tryptophan hydroxylases 1 and 2, respectively; Trp, tryptamine.sss