Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland

• Published in: Life sciences (1973) 2008-01, Vol.82 (1), p.108-114
• Main Authors: Garcia, Rodrigo Antonio Peliciari, Afeche, Solange Castro, Scialfa, Julieta Helena, do Amaral, Fernanda Gaspar, dos Santos, Sabrina Heloísa José, Lima, Fabio Bessa, Young, Martin Elliot, Cipolla-Neto, José
• Format: Article
• Language: English
• Subjects: Acetylserotonin O-Methyltransferase - genetics; Acetylserotonin O-Methyltransferase - metabolism; Animals; Aralkylamine N-acetyltransferase; Arylalkylamine N-Acetyltransferase - genetics; Arylalkylamine N-Acetyltransferase - metabolism; Arylalkylamine- N-acetyltransferase; Circadian Rhythm - physiology; Circadian rhythms; Fibers; Gene expression; Gene Expression - drug effects; Hydroxyindol- O-methyltransferase; In Vitro Techniques; Innervation; Insulin; Insulin - pharmacology; Insulin - physiology; Male; Melatonin; Melatonin - biosynthesis; Norepinephrine; Norepinephrine - pharmacology; Norepinephrine - physiology; Pineal gland; Pineal Gland - drug effects; Pineal Gland - enzymology; Pineal Gland - metabolism; Post-transcription; Protein Processing, Post-Translational; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Secretion; Tryptophan hydroxylase; Tryptophan Hydroxylase - genetics; Tryptophan Hydroxylase - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2007.10.016

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 − 8M) 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.