Modified Model of Hypothyroidism During the Preweanling Period

Abstract

Propylthiouracil (PTU) has received widespread use as a means of inducing hypothyroidism in experimental animals. Doses of PTU used in these studies are high (doses of 200 mg/kg are frequently cited) and no reference is made as to the degree of hypothyroidism attained. Experiments were conducted to determine the minimum dose of PTU required to maximally suppress plasma thyroid hormone levels in the developing rat. It was found that PTU doses of 8.8 mg/kg body weight provide maximal suppression of plasma thyroid hormone levels. This dose of PTU was also shown to inhibit Purkinje cell dendritic maturation in the cerebellum, a hallmark of congenital hypothyroidism. The brain and body weight deficits seen with a PTU dose of 8.8 mg/kg were eliminated using physiological replacement doses of L-thyroxine. These results indicate that doses of PTU used in typical hypothyroid models are far in excess of what is required to induce hypothyroidism in the developing rat. Consequently, the lower doses of PTU identified in this study can be utilized to achieve maximal suppression of thyroid hormone levels, reducing the possibility of potential nonspecific effects of higher doses.