Administration of triiodo-L-thyronine into dorsal hippocampus alters phosphorylation of Akt, mammalian target of rapamycin, p70S6 kinase and 4E-BP1 in rats.
Thyroid hormones play critical roles in brain functions. The underlying mechanisms remain unknown but classical regulation of gene expression through binding to nuclear thyroid hormone receptors has been widely implicated. Evidence has also accumulated suggesting that thyroid hormone can exert effects through non-classical mechanisms involving activation of signal transduction pathways. Whether thyroid hormone can activate signal transduction pathways in the brain is not fully understood. In this study, we administrated 3,5,3'-triiodo-L: -thyronine (T3) into rat dorsal hippocampus and determined the phosphorylation of Akt and its downstream targets, mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6k) and the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) signaling molecules. T3 caused specific rapid and persistent activation of phosphatidylinositol 3-kinase (PI3K)/Akt-mTOR signaling pathway, which was mediated by thyroid hormone receptors. Furthermore, the rapid action of T3 did not require protein or RNA synthesis, whereas, the persistent action of T3 was translational and transcriptional activities-dependent. These findings indicated that activation of PI3K/Akt-mTOR signaling pathway provides a new molecular mechanism for thyroid hormone actions in the hippocampus and this new mechanism may contribute to some effects of thyroid hormones in the central nervous system.
Sui
Li
L
Institute of Neurobiology, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. lsui@fudan.edu.cn
Wang
Jing
J
Li
Bao-Ming
BM
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D014284:Triiodothyronine / Q000008:administration & dosage / Q000378:metabolism
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D011988:Receptors, Thyroid Hormone; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D014284:Triiodothyronine; C499526:Eif4ebp1 protein, rat; C546845:mTOR protein, rat