Corticosterone modulates noradrenaline-induced melatonin synthesis through inhibition of nuclear factor kappa B.
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 microm) for 48 hr in the presence or absence of the glucocorticoid receptor (GR) antagonist, mifepristone (1.0 microm), the proteasome inhibitor, N-acetyl-leucinyl-leucinyl-norleucinal-H (ALLN, 12.5 microm) or the antagonist of the nuclear factor kappa B (NFkappaB), pyrrolidinedithiocarbamate (PDTC, 12.5 microm). 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 microm corticosterone was blocked by mifepristone, and mimicked by ALLN and PDTC. The presence of GRs was shown by [3H]-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.
Ferreira
Zulma S
ZS
Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, Universidade de São Paulo, São Paulo, Brazil.
Fernandes
Pedro A C M
PA
Duma
Danielle
D
Assreuy
Jamil
J
Avellar
Maria C W
MC
Markus
Regina P
RP
D000818:Animals; D001483:Base Sequence; D003345:Corticosterone / Q000494:pharmacology*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D015735:Mifepristone / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D009638:Norepinephrine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000031:analogs & derivatives* / Q000096:biosynthesis; D013859:Thiocarbamates / Q000494:pharmacology
D006727:Hormone Antagonists; D007976:Leupeptins; D016328:NF-kappa B; D011759:Pyrrolidines; D011965:Receptors, Glucocorticoid; D013859:Thiocarbamates; C063261:acetylleucyl-leucyl-norleucinal; C020972:pyrrolidine dithiocarbamic acid; D015735:Mifepristone; D012701:Serotonin; D003907:Dexamethasone; D004247:DNA; D008550:Melatonin; C006389:N-acetylserotonin; D003345:Corticosterone; D009638:Norepinephrine