l-Triiodothyronine differentially and nongenomically regulates synaptosomal protein phosphorylation in adult rat brain cerebral cortex: Role of calcium and calmodulin

“Quo Vadis?” Deciphering the Code of Nongenomic Action of Thyroid Hormones in Mature Mammalian Brain

“…Effects of TH on Ca 2+ -dependent activation of PKC and/or Ca 2+ /CaMdependent protein kinases are also possible, followed by direct or indirect activation of phosphorylation of the proteins. Thus further investigation demonstrated for the first time the rapid nongenomic second messenger mediated regulation of protein phosphorylation by TH in mature mammalian brain and provided additional support for the contention that TH has a unique and complex signaling function in adult brain [12].…”

“…Determination of whether activation or inactivation of a specific type(s) of G-protein influences TH-effects on protein phosphorylation is crucial. A diverse nongenomic effect of TH has been observed in non-neural tissues including liver, heart, adipocytes, and blood [12,68]. Some possible nongenomic actions of THs include modulation of GABA uptake, regulation of NKA activity and increase of presynaptic Ca 2+influx.…”

“…THs also promote MAPK-mediated serine phosphorylation of the nuclear TH receptor β-1 isoform nongenomically in 293T cells. Ca 2+ and CaM also differentially regulate of THinduced neuronal protein phosphorylation [12,87].…”

“…Thus, besides the genomic concepts, a parallel idea of nongenomic of TH action was emerging with demonstration of direct plasma membrane-TH interaction and expression of some hormonal effects in a variety of cells. These studies include activation on Ca 2+ -ATPase in red blood cells, acetylcholinesterase in neuronal plasma membrane, inhibition of synaptosomal membrane Na + -K + -ATPase (NKA), rapid action of L-T3 on synaptosomal Ca 2+influx, identification of specific L-T3-binding sites in rat thymocyte membrane, synaptosomal membrane, depolarization of actin filaments in cultured astrocytes by TH, and changes in second messengers and their corresponding regulatory systems following TH treatment [1,11,12].…”

Synaptic and Non-Synaptic Mitochondria in Hippocampus of Adult Rats Differ in Their Sensitivity to Hypothyroidism

“…It was found that the administration of thyroid hormones causes upregulation of several genes, including the genes participating in circadian regulation and in regulation of signaling pathways (Diez et al 2008). Nongenomic action of thyroid hormones includes modulation of neuronal excitability (Caria et al 2009) and oxidative energy metabolism (Katyare and Rajan 2005), prevention against NMDA-receptors dependent neuronal damage (Alva-Sánchez et al 2009), and regulation of synaptosomal protein phosphorylation (Sarkar 2008). An overall decline in the metabolic activity of the hypothyroid brain compared with euthyroid brain was observed, characteristically manifested in energy metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis (Constantinou et al 2011).…”