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Stimulation role of epinephrine in transcription of the melatonin synthesis key enzyme AANAT in the pineal gland of broilers


Melatonin is a crucial neurohormone synthesized in the pineal gland that influences the physiology of animals. The molecular mechanism of norepinephrine control of the synthesis of melatonin is well documented; however, few reports have described the effects of epinephrine on the synthesis of melatonin. In this study, the effect of epinephrine on melatonin synthesis was investigated by adding different concentrations of epinephrine or norepinephrine to broiler pineal glands cultured in vitro. In addition, we investigated how epinephrine regulates the synthesis of melatonin and the transcription of the key melatonin synthesis enzyme AANAT. We determined the abundance of melatonin, norepinephrine, and epinephrine in broiler serum and the mRNA expression levels of key enzymes under different light conditions. The minimum concentrations of epinephrine and norepinephrine required to recover the melatonin synthesis rhythm in pineal cells were 10−13 and 10−11 mol/L, respectively. Under various light durations, epinephrine reached maximum levels two hours earlier than melatonin. These results demonstrate for the first time that epinephrine can increase the synthesis of melatonin by increasing the transcription of AANAT.

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  1. Munch M, Schmieder M, Bieler K, Goldbach R, Fuhrmann T, Zumstein N, Vonmoos P, Scartezzini JL, Wirz-Justice A, Cajochen C (2017) Bright light delights: effects of daily light exposure on emotions, rest-activity cycles, sleep and melatonin secretion in severely demented patients. Curr Alzheimer Res 14:1063–1075.

    CAS  Article  PubMed  Google Scholar 

  2. Kang JT, Koo OJ, Kwon DK, Park HJ, Jang G, Kang SK, Lee BC (2009) Effects of melatonin on in vitro maturation of porcine oocyte and expression of melatonin receptor RNA in cumulus and granulosa cells. J Pineal Res 46(1):22–28.

    Article  CAS  PubMed  Google Scholar 

  3. Jaworek J, Szklarczyk J, Jaworek AK, Nawrot-Porabka K, Leja-Szpak A, Bonior J, Kot M (2012) Protective effect of melatonin on acute pancreatitis. Int J Inflam.

    Article  PubMed  PubMed Central  Google Scholar 

  4.  Hardeland R (2008) Melatonin, hormone of darkness and more: occurrence, control mechanisms, actions and bioactive metabolites. Cell Mol Life Sci 65(13):2001–2018.

    Article  CAS  PubMed  Google Scholar 

  5. Stebelová K, Anttila K, Mänttäri S, Saarela S, Zeman M (2010) Immunohistochemical definition of MT2 receptors and melatonin in the gastrointestinal tissues of rat. Acta Histochemica 112(1):26–33.

    Article  CAS  PubMed  Google Scholar 

  6. Isobe Y, Fujioi J, Nishino H (2001) Circadian rhythm of melatonin release in pineal gland culture: arg-vasopressin inhibits melatonin release. Brain Res 918(1–2):67–73.

    Article  CAS  PubMed  Google Scholar 

  7. Klein DC, Weller JL (1970) Indole metabolism in the pineal gland: a circadian rhythm in N-acetyltransferase. Sci 169(3950):1093-1095.

    Article  CAS  Google Scholar 

  8. Stehle JH, von Gall C, Schomerus C, Korf HW (2001) Of rodents and ungulates and melatonin: creating a uniform code for darkness by different signaling mechanisms. J Biol Rhythms 16(4):312–325.

    Article  CAS  PubMed  Google Scholar 

  9. Zatz M, Gastel JA, Heath JR, Klein DC (2000) Chick Pineal Melatonin Synthesiss : light and cyclic AMP control abundance of serotonin N-acetyltransferase protein. J Neurochem 74(6):2315–2321.

    Article  CAS  PubMed  Google Scholar 

  10. Rey E, Hernandez-Diaz FJ, Abreu P, Alonso R, Tabares L (2001) Dopamine induces intracellular Ca2+ signals mediated by alpha1B-adrenoceptors in rat pineal cells. Euro J Pharmacol 430:9–17.

    Article  CAS  Google Scholar 

  11. Zatz M, Mullen DA (1988) Norepinephrine, acting via adenylate cyclase, inhibits melatonin output but does not phase-shift the pacemaker in cultured chick pineal cells. Brain Res 450:137–143.

    Article  CAS  PubMed  Google Scholar 

  12. Vaudry D, Gonzalez BJ, Basille M, Yon L, Fournier A, Vaudry H (2000) Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol Rev 52(2):269–324

    CAS  PubMed  Google Scholar 

  13. Albarran MT, Lopez-Burillo S, Pablos MI, Reiter RJ, Agapito MT (2001) Endogenous rhythms of melatonin, total antioxidant status and superoxide dismutase activity in several tissues of chick and their inhibition by light. J Pineal Res 30(4):227–233.

    Article  CAS  PubMed  Google Scholar 

  14. Claudia C, Lucia F, Estela M, Morten M, Lilian P (2008) Daily rhythms of norepinephrine, β1-adrenoceptor mRNA, serotonin, arylalkylamine N-acetyltransferase mRNA, arylalkylamine N-acetyltransferase and hydroxyindol-O-methyltransferase activities, and melatonin in the pineal gland of viscacha. Biol Rhythm Res 39(2):93–107.

    Article  CAS  Google Scholar 

  15. Simonneaux V, Ribelayga C (2003) Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev 55(2):325–395.

    Article  CAS  PubMed  Google Scholar 

  16. Peliciari-Garcia RA, Andrade-Silva J, Cipolla-Neto J, Carvalho CR (2013) Leptin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland. Biomed Res Int 2013:546516.

  17. Chong NW, Bernard M, Klein DC (2000) Characterization of the chicken serotonin N-acetyltransferase gene. Activation via clock gene heterodimer/E box interaction. J biol chem 275(42):32991–32998.

    Article  CAS  PubMed  Google Scholar 

  18. Rohde K, Rovsing L, Ho AK, Moller M, Rath MF (2014) Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat pineal gland and its role in regulation of arylalkylamine N-acetyltransferase (AANAT). Endocrinol 155 (8):2966–2975.

    Article  CAS  Google Scholar 

  19. Goyal RN, Aziz MA, Oyama M, Chatterjee S, Rana ARS (2011) Nanogold based electrochemical sensor for determination of norepinephrine in biological fluids. Sens Actuators B: Chem 153(1):232–238.

    Article  CAS  Google Scholar 

  20. Shahrokhian S, Ghalkhani M, Amini MK (2009) Application of carbon-paste electrode modified with iron phthalocyanine for voltammetric determination of epinephrine in the presence of ascorbic acid and uric acid. Sens Actuators B: Chem 137(2):669–675.

    Article  CAS  Google Scholar 

  21. Zatz M, Mullen Da Fau - Moskal JR, Moskal JR (1988) Photoendocrine transduction in cultured chick pineal cells: effects of light, dark, and potassium on the melatonin rhythm. Brain Res 438:199–215.

    Article  CAS  PubMed  Google Scholar 

  22. Livak KJ, Schmittgen TD (2001) Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods 25(4):402–408.

    Article  CAS  Google Scholar 

  23. Wengrowski AM, Wang X, Tapa S, Posnack NG, Mendelowitz D, Kay MW (2015) Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function. Cardiovasc Res 105(2):143–150.

    Article  CAS  PubMed  Google Scholar 

  24. Fu Z, Kato H, Sugahara K, Kubo T (2008) Circadian Rhythm of Pineal Melatonin in Silky Chicks. Jan Poult Sci 35(1):55–59.

    Article  Google Scholar 

  25.  Rosy, Yadav SK, Agrawal B, Oyama M, Goyal RN (2014) Graphene modified Palladium sensor for electrochemical analysis of norepinephrine in pharmaceuticals and biological fluids. Electrochimica Acta 125:622–629.

    Article  CAS  Google Scholar 

  26. Nadiki HH, Noroozifar M, Khorasani-Motlagh M (2014) Development of glassy carbon electrode modified with ruthenium red-multiwalled carbon nanotubes for simultaneous determination of epinephrine and acetaminophen. Anal sci 30:911–918.

    Article  CAS  PubMed  Google Scholar 

  27. Harpsøe NG, Andersen LPH, Gögenur I, Rosenberg J (2015) Clinical pharmacokinetics of melatonin: a systematic review. Eur J Clin Pharmacol 71:901–909.

    Article  CAS  PubMed  Google Scholar 

  28. Wang M, Yokotani K, Nakamura K, Murakami Y, Okada S, Osumi Y (1999) Melatonin inhibits the central sympatho-adrenomedullary outflow in rats. Jan J Pharmacol 81:29–33.

    Article  CAS  Google Scholar 

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The Scientific and Technological Research Project in Henan Province (Grant Nos. 162102210297 and 172102110034), Major Scientific and Technological Project in Henan Province (Grant No. 141100110800), and Key Research Projects of Higher Education in Henan Province (Grant No. 17A230011) supported this work.

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Authors and Affiliations



JL participated in conceiving and designing the study. YW performed most of the experiments, analyzed the data, and wrote the manuscript. ZZ, HG, PL, and QL participated in several of the experiments. All the authors discussed and approved the final manuscript.

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Correspondence to Jingang Li.

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The authors declare no conflicts of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Wang, Y., Zhang, Z., Guo, H. et al. Stimulation role of epinephrine in transcription of the melatonin synthesis key enzyme AANAT in the pineal gland of broilers. Mol Cell Biochem 453, 111–119 (2019).

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  • Melatonin (MLT)
  • Epinephrine (E)
  • Pineal gland
  • Broilers