glutaminase and Hypothyroidism

Thyroid hormones modulate the physiology of the hippocampus in humans, where glutamate plays an important role as neurotransmitter. The aim of this work was to study the effect of hypothyroidism on hippocampal glutamate extracellular levels, release, uptake, and synthesis. The effects of PDC (a glutamate transporter inhibitor) and ouabain (a Na(+) /K(+) -ATPase inhibitor) infusion on microdialysate glutamate and aspartate levels of CA3 hippocampal region were evaluated. Animals were assigned to one of the following groups: hypothyroid group (Hyp), receiving methimazole (anantithyroid drug); replacement group (Hyp + T(4) ), receiving antithyroid treatment plus thyroxine; and euthyroid control group (Eut). Dialysate fractions were collected every 15 min to determine basal glutamate levels for 1 hr. Then, PDC (10 mM) or ouabain (100 μM) was infused for 30 min. Results showed lower glutamate and aspartate basal levels in Hyp than in Eut groups. PDC infusion increased amino acids levels in all groups, whereas ouabain infusion increased glutamate and aspartate levels only in the Eut group. The infusion of tetrodotoxin (TTX; a voltage-gated sodium channel inhibitor) prevented the glutamate increase in euthyroid rats. The Hyp + T(4) group showed glutamate levels similar to those found in the Eut group. Additionally, glutaminase activity in hippocampus was lower in the Hyp group than in the Eut or Hyp + T(4) group. Results suggest that high-affinity glutamate transporters are not altered by hypothyroidism; however, decreased hypotyroidism reduced vesicular glutamate release in the CA3-hippocampal region as a consequence of diminished glutamate synthesis.

Topics: Analysis of Variance; Animals; Antithyroid Agents; Aspartic Acid; CA3 Region, Hippocampal; Drug Interactions; Enzyme Inhibitors; Glutamate-Ammonia Ligase; Glutamic Acid; Glutaminase; Hypothyroidism; Male; Methimazole; Microdialysis; Neurotransmitter Uptake Inhibitors; Ouabain; Rats; Rats, Wistar; Synapses; Thyroxine

The effect of thyroid hormones on monocyte migration, phagocytic capacity and hydrogen peroxide production by macrophages and the effect of these hormones on glutamine and glucose metabolism was investigated. The experiments were performed on resident, thioglycollate- and BCG-stimulated cells from hypo- and hyperthyroid rats. High plasma levels of thyroid hormones suppressed the migration of monocytes and hydrogen peroxide production, whereas hypothyroidism did not affect cell migration but raised the phagocytic capacity and the hydrogen peroxide production. Hyperthyroidism increased the activities of glutaminase and hexokinase and the rates of decarboxylation of [U-14C]-glutamine and [U-14C]-glucose in inflammatory and activated cells. Hypothyroidism stimulated glucose metabolism and had only a slight effect on glutaminolysis. The activity of the TCA cycle was, however, diminished in the presence of high plasma levels of thyroid hormones and enhanced by the hypothyroid state. These findings suggest that the functional changes are more likely to be related to the activity of the TCA cycle rather than to glutaminolysis and glycolysis.

Topics: Animals; Cell Movement; Citrate (si)-Synthase; Decarboxylation; Glucose; Glutaminase; Glutamine; Hexokinase; Hydrogen Peroxide; Hyperthyroidism; Hypothyroidism; Lactates; Macrophages, Peritoneal; Male; Mycobacterium bovis; Phagocytosis; Rats; Rats, Wistar; Thioglycolates

The effect of thyroid deficiency on the activity of phosphate-activated glutaminase (the marker for glutamatergic neurons) was studied in different parts of the rat brain at ages 5, 10, 15 and 25 days, and at day 130 following 102 days of rehabilitation. The brain regions investigated were the cerebral cortex, basal forebrain, hippocampus and cerebellum. During normal development, the activity of glutaminase increased relatively earlier in the cerebral cortex and hippocampus than in the cerebellum, while the absolute value reached a much higher level in the hippocampus than in other brain regions. In the basal forebrain, the developmental pattern of glutaminase was bimodal, and the rise in enzyme activity after 15 days coincided with the decrease in the cerebral cortex. These regional developmental changes in glutaminase activity correlated well with known information on the formation of glutamatergic cells and pathways in the brain. Neonatal thyroid deficiency had little effect on the developmental patterns of enzyme activity, the exception being a transient decrease in 10-day-old hypothyroid hippocampus. The present results, together with previous findings, indicate that the effect of thyroid hormone on neural maturation is cell-type specific and the glutamatergic neurons are not the main targets of thyroid hormone action.

Topics: Aging; Animals; Brain; Glutaminase; Hypothyroidism; Propylthiouracil; Rats; Thyroid Hormones

Topics: Ammonia; Animals; Antithyroid Agents; Aspartic Acid; Dactinomycin; Depression, Chemical; Diet; Ethionine; Glutaminase; Glutamine; Hyperthyroidism; Hypothyroidism; Kidney; Ligases; Liver; Male; Ornithine; Phosphotransferases; Propylthiouracil; Puromycin; Rats; Stimulation, Chemical; Thyroid Hormones; Transaminases; Transferases; Urea

Topics: Amidohydrolases; Ammonia; Animals; Glutamate Dehydrogenase; Glutamates; Glutaminase; Hyperthyroidism; Hypothyroidism; Kidney; Liver; Propylthiouracil; Rats