Effects of altered thyroid states and undernutrition on the calbindin-D28K (calcium-binding protein) content of the hippocampal formation in the developing rat

A quantitative study of calbindin-D28K (calcium-binding protein) was carried out on the developing hippocampal formation in normal, hypothyroid, hyperthyroid, and underfed rats. In normal animals, the calbindin-D28K content increased after birth in agreement with the distribution of the protein previously reported by immunocytochemistry. Calbindin-D28K was strikingly spared, compared to the other proteins, from the effects of hypothyroidism. On the contrary, the calbindin-D28K:protein ratio was transiently reduced by hyperthyroidism. Corrective doses of thyroxine to hypothyroid rats increased the calbindin-D28K content whatever the period of the hormonal treatment, but they also had a marked effect on the hippocampal weight and the protein content, especially when the hormone was given on days 2-3. With this latter replacement therapy schedule, the calbindin-D28K:protein ratio dropped from the high value of the hypothyroid animal to normal. Taken together, the results obtained in hypothyroidism, hyperthyroidism and replacement therapy are consistent with a pronounced action of thyroid hormone on hippocampal structures other than those containing calbindin-D28K. Undernutrition, which, like hypo- or hyperthyroidism, also markedly impairs hippocampal growth, affected the calbindin-D28K content per hippocampus but not the calbindin-D28K:protein ratio. This emphasizes the unique influence of thyroid hormone on brain development. The relative preservation of calbindin-D28K in the hippocampal formation of animals lacking thyroid hormone suggests that calbindin-D28K function may be crucial in this brain region.