Thyrotropin Regulation by Thyroid Hormone in Thyroid Hormone Receptor β-Deficient Mice1

Thyroid hormone responsive genes can be both positively and negatively regulated by thyroid hormone. TSH is down-regulated by thyroid hormone and rises during thyroid hormone deprivation. Because both thyroid hormone receptor (TR) α and β genes are expressed in the pituitary gland, it is unclear what the relative roles of TRα and TRβ are in TSH regulation. Experiments using over expression of artificial genes have yielded conflicting results. The TRβ knock-out mouse that lacks both TRβ1 and TRβ2 isoforms provides a model to examine the role of these receptors in TSH regulation. TRβ deficient (TRβ−/−) and wild-type (TRβ+/+) mice of the same strain were deprived of thyroid hormone by feeding them a low iodine diet containing propylthiouracil and were then treated with different doses of L-T3 and L-T4. Thyroid hormone deprivation rapidly increased the serum TSH level in both TRβ+/+ and TRβ−/− mice, reaching a similar level in the absence of thyroid hormone. In contrast, the decline of serum TSH by treatment ...