SUBCELLULAR-DISTRIBUTION OF CARBONIC-ANHYDRASE AND NA-ATPASE IN THE BRAIN OF THE HYT HYT HYPOTHYROID MICE(,K+)

Activities of carbonic anhydrase and Na+,K+-ATPase in tissue homogenat es and in subcellular fractions from different brain regions were stud ied in inherited primary hypothyroid (hyt/hyt) mice. The body weight, the weight of different brain regions, and the plasma thyroxine and tr iiodothyronine levels of hyt/hyt mice were significantly lower than th ose of the age-matched hyt/+ controls. In tissue homogenates of cerebr al cortex, brain stem and cerebellum of hypothyroid mice, the activity of carbonic anhydrase (units/mg protein) was 59.2, 57.6, and 43.2%, a nd the activity of Na+,K+-ATTase (nmol Pi/mg protein/min) was 73.7, 74 .4 and 68.7%, respectively, of that in corresponding regions of euthyr oid littermates. The decrease in enzyme activity in tissue homogenates was also reflected in different subcellular fractions. In cerebral co rtex and brain stem, carbonic anhydrase activity in cytosol, myelin an d mitochondrial fractions of hypothyroid mice was about 45-50% of that in euthyroid mice, while in cerebellum the carbonic anhydrase activit y in these subcellular fractions of hyt/hyt mice was only 33-38% of th at in hyt/+ controls. Na+,K+-ATPase activity in myelin fraction of dif ferent brain regions of hyt/hyt mice was about 34-42% of that in hyt/ mice, while in mitochondria, synaptosome and microsome fractions were about 44-52, 46-53, and 66-68%, respectively of controls. These data indicate that the activity of both carbonic anhydrase and Na+,K+-ATPas e was affected more in the myelin than other subcellular fractions and more in the cerebellum than cerebral cortex and brain stem by deficie ncy of thyroid hormones. A reduction in the activity of transport enzy mes in brain tissues as a result of thyroid hormone deficiency during the critical period of development may underlie permanent nervous diso rders in primary hypothyroidism.