Regulation of the the rat pineal gland hormonal production by modulators of the inflammatory process

Author(s)

Pedro Augusto Carlos Magno Fernandes

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2009-03-12

Examining board members

Regina Pekelmann Markus; Jamil Assreuy Filho; Rui Curi; Cláudia Lúcia Martins da Silva; Mari Cleide Sogayar

• Advisor: Regina Pekelmann Markus; Valérie Simonneaux

Abstract

The melatonin, synthetized by the pineal gland, exihibits a number of regulatory activities on the internal dynamic homeostasis of mammals. These functions are related to the regulation of endogenous circadian and seasonal rhythms during healthy and physiopathological processes. This study evaluates the effects of the inflammatory modulators, corticosterone, TNF and IFN- y, over the pineal gland metabolism. The results presented here show that: 1 - Corticosterone enhances the synthesis of norepinephrine in vivo and in vitro in the presence of β-adrenergic stimulation, but inhibits the hormonal production when both, αand βadrenoceptors, are activated. 2 - This effect depends on the GR activation and does not interfere in the extraneuronal uptake of catecholamines. 3 - Corticosterone increases the expression of the aanat transcript and also the enzymatic activity of AA-NAT and HIOMT. 4 - Corticosterone inhibits the nuclear accumulation of NF-κB. 5 - The pharmacological inhibition of NF-κB pathway mimics the effect of corticosterone on the hormonal production in pineal. 6 - IFN-y inhibits the NF- κB pathway. 7 - IFN-y enhances the synthesis of melatonin in the pineal gland. 8- TNF activates the NF-κB pathway. 9 - TNF inhibits the production of melatonin in the pineal gland. 10 - TNF transiently inhibits the production of the aa-nat transcript and also of NAS. 11 - This transient effect depends on the synthesis of proteins. This study shows that the pineal gland can respond to different inflammatory modulators, supporting the hypothesis of a central immune-pineal axis controlling pathological processes in mammals. . (AU)