Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland.
The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking during the dark phase. This synthesis is primarily regulated by sympathetic innervations via noradrenergic fibers, but is also modulated by many peptidergic and hormonal systems. A growing number of studies reveal a complex role for melatonin in influencing various physiological processes, including modulation of insulin secretion and action. In contrast, a role for insulin as a modulator of melatonin synthesis has not been investigated previously. The aim of the current study was to determine whether insulin modulates norepinephrine (NE)-mediated melatonin synthesis. The results demonstrate that insulin (10(- 8)M) potentiated norepinephrine-mediated melatonin synthesis and tryptophan hydroxylase (TPOH) activity in ex vivo incubated pineal glands. When ex vivo incubated pineal glands were synchronized (12h NE-stimulation, followed by 12h incubation in the absence of NE), insulin potentiated NE-mediated melatonin synthesis and arylalkylamine-N-acetyltransferase (AANAT) activity. Insulin did not affect the activity of hydroxyindole-O-methyltranferase (HIOMT), nor the gene expression of tpoh, aanat, or hiomt, under any of the conditions investigated. We conclude that insulin potentiates NE-mediated melatonin synthesis in cultured rat pineal gland, potentially through post-transcriptional events.
University of São Paulo, Institute of Biomedical Sciences, Department of Physiology and Biophysics, Av. Prof. Lineu Prestes 1524, 1st floor, room 118, Sao Paulo, SP, CEP 05508-900, Brazil.
Rodrigo Antonio Peliciari
RA
Garcia
Solange Castro
SC
Afeche
Julieta Helena
JH
Scialfa
Fernanda Gaspar
FG
do Amaral
Sabrina Heloísa José
SH
dos Santos
Fabio Bessa
FB
Lima
Martin Elliot
ME
Young
José
J
Cipolla-Neto
D000121:Acetylserotonin O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology; D010870:Pineal Gland / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
D007328:Insulin; D014365:Tryptophan Hydroxylase; D000121:Acetylserotonin O-Methyltransferase; C520223:Aanat protein, rat; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin; D009638:Norepinephrine