"Short" Loop Feedback Regulation of Hypothalamic and Brain Thyrotropin-Releasing Hormone Content in the Rat and Dwarf Mouse*

In order to determine whether T4, TSH, or both affect hypothalamic TRH content, primary or secondary hypothyroidism was induced in the rat by thyroidectomy (Tx) or hypophysectomy (Hx), respectively. Two weeks later, rats were treated with T4, TSH, or both for 14--16 days. Tx or Hx significantly decreased hypothalamic TRH content, and T4 treatment restored hypothalamic TRH to normal in the Tx but not in the Hx rats. When TSH was administered simultaneously with T4 to Hx rats, hypothalamic TRH content was restored to normal. Whole brain TRH content was not affected by Tx, Hx, or by the various treatment regimens. Similar experiments were performed in Snell dwarf (dw/dw) mice. Hypothalamic TRH content was significantly decreased when compared to normal litter mates (dw/+). As in Hx rats, T4 administration to dw/dw mice for 16 days did not restore hypothalamic TRH content to normal. Brain TRH content was similar in both groups and was not altered by T4 treatment. It is concluded that T4 affects hypothalamic TRH content, but that TSH is required for this T4 effect. Whole brain TRH, on the other hand, is unaffected by any of these alterations in thyroid-pituitary function.