Increased sensitivity of the thyrotroph to thyrotropin-releasing hormones in rats with hypothalamic hypothyroidism

The status of TSH secretion in hypothalamic hypothyroidism was evaluated by using rats with anterior medial basal hypothalamic deafferentation as the experimental model of the disorder. In the deafferented rats, the basal serum thyroid hormone concentrations as well as that of TSH was significantly lower than normal and cold exposure failed to increase serum TSH, indicating they were in fact in a hypothalamic hypothyroid state. The minimum effective dose of TRH to elicit an increase in serum TSH was smaller in the deafferented rats than in the controls, whereas the response to the maximum dose of TRH was similar in both groups. Although the radioimmunoassayable TSH of the adenohypophysis was significantly decreased in the deafferented rats, it was qualitatively similar to that of the control rats, since the peak of TSH immunoreactivity was eluted at exactly the same position on the gel filtration column in the pituitaries from normal and deafferented rats. When the adenohypophysis was perifused in vitro with Krebs-Ringer solution buffered with Hepes, the minimum effective dose of TRH was similar in both cases. This finding suggests that the exposure to the perifusion medium completely devoid of thyroid and hypothalamic hormones erased the difference in sensitivity to TRH between the two groups as observed in vivo, although in vivo experiments on deafferented rats with normal thyroid hormone induced by exogenous thyroid hormone were not performed. Our results indicate that in hypothalamic hypothyroid rats: 1) the sensitivity but not the responsiveness of the thyrotroph to TRH is increased; and 2) the readily releasable fraction of pituitary TSH pool in response to exogenous TRH is increased. It is also suggested that the difference in the milieu between the pituitary of normal and deafferented rats in vivo is critically important for the latter to retain hypersensitivity to TRH.