Thyroid Hormones Influence the Development of Hippocampal Glucocorticoid Receptors in the Rat: A Mechanism for the Effects of Postnatal Handling on the Development of the Adrenocortical Stress Response

The role of thyroid hormones on the development of intracellular glucocorticoid receptor concentrations was examined in the hippocampus, hypothalamus, and pituitary of the rat. Adult animals, administered triiodothyronine (T3; 1.0 micrograms/g body weight) on days 1, 2, and 4 of life or thyroxine (T4; 2.5 micrograms/g body weight) on days 1 and 2 of life, had significantly elevated glucocorticoid receptor concentrations in the hippocampus, but not in hypothalamus or pituitary. Adult animals treated with propylthiouracil (PTU; 0.2% in the mother's food), a thyroid hormone synthesis inhibitor, for the first 2 weeks of life showed decreased glucocorticoid receptor concentrations in hippocampus, but not in hypothalamus or pituitary. We then examined whether thyroid hormones might mediate the effects of early stimulation on the development of hippocampal glucocorticoid receptor concentrations. Animals that were handled for 15 min daily (Ha) for the first 2 weeks of life showed increased hippocampal glucocorticoid receptor concentrations as adults compared to nonhandled (NHa) controls. PTU administration blocked the effects of handling, such that Ha/PTU animals showed hippocampal glucocorticoid receptor concentrations that were indistinguishable from those of NHa animals. In contrast, corticosterone administration over the first 2 weeks of life had no effect on adult hippocampal glucocorticoid receptor concentrations. These data suggest that thyroid hormones mediate, in part at least, the development of glucocorticoid receptor concentrations in the hippocampus and that this effect occurs independently of their effects on corticosterone titers.