Corticosterone modulates noradrenaline-induced melatonin synthesis through inhibition of nuclear factor kappa B

Corticosterone modulates noradrenaline-induced melatonin synthesis through inhibition of nuclear factor kappa B

Author Ferreira, Z. S. Google Scholar
Fernandes, PACM Google Scholar
Duma, D. Google Scholar
Assreuy, J. Google Scholar
Avellar, MCW Google Scholar
Markus, R. P. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de Santa Catarina (UFSC)
Universidade Federal de São Paulo (UNIFESP)
Abstract In chronically inflamed animals, adrenal hormones exert a positive control on the secretion of melatonin by the pineal gland. in this paper, the mechanism of corticosterone as a modulator of melatonin and N-acetylserotonin (NAS) was determined. Rat pineal glands in culture, stimulated for 5 hr with noradrenaline (10 nm), were previously incubated with corticosterone (1.0 nm-1.0 mum) for 48 hr in the presence or absence of the glucocorticoid receptor (GR) antagonist, mifepristone (1.0 mum), the proteasome inhibitor, N-acetyl-leucinyl-leucinyl-norleucinal-H (ALLN, 12.5 mum) or the antagonist of the nuclear factor kappa B (NFkappaB), pyrrolidinedithiocarbamate (PDTC, 12.5 mum). Corticosterone potentiated noradrenaline-induced melatonin and NAS production in a bell-shaped manner. the increase in NAS (12.9 +/- 2.7, n = 6 versus 34.3 +/- 8.3 ng per pineal) and melatonin (16.3 +/- 2.0, n = 6 versus 44.3 +/- 12.9 ng per pineal) content induced by 1 mum corticosterone was blocked by mifepristone, and mimicked by ALLN and PDTC. the presence of GRs was shown by [H-3]-dexamethasone binding (0.30 +/- 0.09 pmol/mg protein) and corticosterone inhibition of NFkappaB nuclear translocation was demonstrated by electromobility shift assay. Therefore, corticosterone potentiates noradrenaline-induced melatonin and NAS production through GR inhibition of NFkappaB nuclear translocation. To the best of our knowledge, this is the first time that this relevant pathway for passive and acquired immune response is shown to modulate melatonin production in pineal gland.
Keywords corticosterone
extraneuronal uptake
melatonin
N-acetylserotonin
NF kappa B
pineal gland
Language English
Date 2005-04-01
Published in Journal of Pineal Research. Copenhagen: Blackwell Munksgaard, v. 38, n. 3, p. 182-188, 2005.
ISSN 0742-3098 (Sherpa/Romeo, impact factor)
Publisher Blackwell Munksgaard
Extent 182-188
Origin http://dx.doi.org/10.1111/j.1600-079X.2004.00191.x
Access rights Closed access
Type Article
Web of Science ID WOS:000227175000007
URI http://repositorio.unifesp.br/handle/11600/28245

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