Regional effects of hypothyroidism on 5′-nucleotidase and cyclic nucleotide phosphohydrolase activities in developing rat brain

Abstract

The activities of 5′-nucleotidase (EC 3.1.3.5) and of 2′,3′-cyclic nucleotide 3′-phosphohydrolase (CNP) (EC 3.1.4.37) were measured in crude membrane preparations from 6 brain regions of hypothyroid rats 31 days and 42 days after conception (8–9 days and 19–20 days after birth respectively) and from normal rats 31, 36 and 42 days after conception. At 42 days the activities of both enzymes were markedly and significantly lower than in controls in all hypothyroid brain regions. The pattern of increase in CNP activity in the brain regions of normal animals reflected the caudo-rostral progress of myelination. At 42 days postconception in the more caudal regions of hypothyroid brain, myelination, as assessed by CNP activity, was delayed by 5–7 days. In the more rostral regions where normal activity had not yet developed, the delay due to hypothyroidism was not clearly defined. The lowered activity of 5′-nucleotidase observed using crude membrane preparations from hypothyroid animals was shown not to be due to a redistribution of enzyme between cytosol and membranes or to losses into the supernatant fraction during preparation of the particulate fraction used for assays. In addition the lowered activity of 5′-nucleotidase could not be accounted for in terms of the delayed myelination and consequent absence of myelin-associated enzyme. In contrast to the results with CNP, the effects of hypothyroidism on 5′-nucleotidase in the 6 regions showed no caudo-rostral pattern. Although it was clear that the lowered activity of 5′-nucleotidase in hypothyroid brain at 20 postnatal days was not directly attributable to the state of delayed myelination, no identification of the structures or cell types affected could be made.