Thyroid hormone regulates oxidative phosphorylation in the cerebral cortex and striatum of neonatal rats.
We have previously shown that thyroid hormone (T(3)) regulates mitochondrial gene expression, morphology and transmembrane potential in the developing brain. Here, we have analysed the effect of thyroid hormone on mitochondrial function in different brain regions. For this purpose we have determined, in control, hypothyroid and T(3)-treated hypothyroid neonatal rats, the rate of oxidative phosphorylation in isolated mitochondria and the activity of the respiratory complexes in tissue homogenates. Our results showed a decrease in oxidative phosphorylation rate (only in the presence of NADH-generating substrates) and mitochondrial complexes I and III activity in the cerebral cortex and striatum of hypothyroid neonates, but not in the other areas analysed (hippocampus, cerebellum, thalamus, mid brain and brain stem). In parallel with mitochondrial activity, the levels of mitochondrially encoded transcripts were decreased only in the cerebral cortex and striatum of hypothyroid rats. The administration of T(3) corrected all these parameters. In summary, this study showed a down-regulation of mitochondrial gene expression accompanied by a decrease in mitochondrial activity in the cerebral cortex and striatum of developing hypothyroid neonatal rats.
Martinez
B
B
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
del Hoyo
P
P
Martin
M A
MA
Arenas
J
J
Perez-Castillo
A
A
Santos
A
A
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents; D002352:Carrier Proteins; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism*; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008713:Methimazole; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D025261:Mitochondrial Proton-Translocating ATPases; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012313:RNA / Q000032:analysis; D000077278:RNA, Mitochondrial; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D013956:Antithyroid Agents; D002352:Carrier Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D000077278:RNA, Mitochondrial; D014284:Triiodothyronine; D008713:Methimazole; D012313:RNA; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; C020439:oligomycin sensitivity-conferring protein