Metabolic control mechanisms in mammalian systems. 8. Thyroid hormone control of alpha-glycerophosphate dehydrogenase activity in rat cerebral cortex and cerebellum.

Abstract

The influence of thyroid hormone on soluble NAD-linked α-glycerophosphate dehydrogenase (α-GPDH) activity as well as the ontogeny and relative distribution of this enzyme were investigated in certain regions of the rat brain. In adult female rats, highest levels of enzyme activity were found in the brain stem and spinal cord; lowest activity was present in the cerebellum. Studies on the development of α-GPDH in the cerebral cortex and cerebellum revealed the presence of extremely low levels of enzyme activity at birth with rapid increases occurring within the first 30 days of life. These developmental increases in α-GPDH activity of the cerebral cortex and cerebellum were markedly impaired in rats made hypothyroid by treatment with 131I at 1 day of age. Whereas 50 μCi of 131I exerted no appreciable effect on the brain enzyme, 60% inhibition of α-GPDH was produced by 200 μCi of the radioisotope. Much less inhibition of enzyme activity in both cerebral cortex and cerebellum was observed when thyroidectomy was delayed for 20 days after birth. Treatment of young hypothyroid animals with L-triiodothyronine (T3) produced increases in cerebrocortical and cerebellar α-GPDH activity which were both time- and dose-dependent. However, when the initiation of T3 treatment was delayed until thyroidectomized animals reached adulthood, the hormone failed to produce any appreciable change in enzyme activity. Cycloheximide, an inhibitor of protein synthesis, prevented the T3-induced increases in brain α-GPDH in neonatally thyroidectomized animals, suggesting that the observed hormone-stimulated increases in enzyme activity may be the result of new enzyme synthesis. Evidence indicates that thyroid hormone plays an important role in the regulation of α-GPDH activity of the developing cerebral cortex and cerebellum.