title: Dual Effect of Catecholamines and Corticosterone Crosstalk on Pineal Gland Melatonin Synthesis.
abstract: OBJECTIVE
  The nocturnal production of melatonin by the pineal gland is triggered by sympathetic activation of adrenoceptors and may be modulated by immunological signals. The effect of glucocorticoids on nocturnal melatonin synthesis is controversial; both stimulatory and inhibitory effects have been reported. During pathophysiological processes, an increased sympathetic tonus could result in different patterns of adrenoceptor activation in the pineal gland. Therefore, in this investigation, we evaluated whether the pattern of adrenergic stimulation of the pineal gland drives the direction of the glucocorticoid effect on melatonin production.
  
  
  METHODS
  The corticosterone effect on the pineal hormonal production induced by β-adrenoceptor or β+α1-adrenoceptor activation was evaluated in cultured glands. We also investigated whether the in vivo lipopolysaccharide (LPS)-induced inhibition of melatonin is dependent on the interaction of glucocorticoids and the α1-adrenoceptor in adrenalectomized animals and on the in vivo blockade of glucocorticoid receptors (GRs) or the α1-adrenoceptor.
  
  
  RESULTS
  Corticosterone potentiated β-adrenoceptor-induced pineal melatonin synthesis, whilst corticosterone-dependent inhibition was observed when melatonin production was induced by β+α1-adrenoceptors agonists. The inhibitory effect of corticosterone is mediated by GR, as it was abolished in the presence of a GR antagonist. Moreover, LPS-induced reduction in melatonin nocturnal plasma content was reversed by adrenalectomy and by antagonizing GR or α1-adrenoceptors.
  
  
  CONCLUSIONS
  The dual effect of corticosterone on pineal melatonin synthesis is determined by the activation pattern of adrenoceptors (β or β+α1) in the gland during GR activation, suggesting that increased activation of the sympathetic system and the hypothalamic-pituitary-adrenal axis are necessary for the control of melatonin production during defense responses.
authors.affiliation: Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Fernandes
authors.forename: Eduardo K
authors.initials: EK
authors.lastname: Tamura
authors.forename: Letícia
authors.initials: L
authors.lastname: D'Argenio-Garcia
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Muxel
authors.forename: Sanseray
authors.initials: S
authors.lastname: da Silveira Cruz-Machado
authors.forename: Marina
authors.initials: M
authors.lastname: Marçola
authors.forename: Cláudia E
authors.initials: CE
authors.lastname: Carvalho-Sousa
authors.forename: Erika
authors.initials: E
authors.lastname: Cecon
authors.forename: Zulma S
authors.initials: ZS
authors.lastname: Ferreira
authors.forename: Regina P
authors.initials: RP
authors.lastname: Markus
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003345:Corticosterone / Q000008:administration & dosage*; D007249:Inflammation / Q000378:metabolism; D007545:Isoproterenol / Q000008:administration & dosage; D008070:Lipopolysaccharides; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D008070:Lipopolysaccharides; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D008550:Melatonin; D007545:Isoproterenol; D003345:Corticosterone