Brain and pituitary receptors for thyrotropin-releasing hormone in hypothyroid rats

The effect of hypothyroidism on the thyrotropin-releasing hormone (TRH) receptors in several brain regions and pituitary of rats was determined. TRH receptors were labeled with 3H-(3-MeHis2)TRH (3H-MeTRH). Hypothyroidism was induced in male Sprague-Dawley rats by administering methimazole (0.05% w/v) in drinking water for 32 days. Rats serving as controls were given water without the methimazole. The development of a hypothyroid state was evidenced by significant decreases in colonic temperature, systolic blood pressure, heart rate and serum concentration of triiodothyronine (total T3), thyroxine and T3 uptake (T3U) as compared to control rats. The rate of gain in body weight of methimazole-treated rats was significantly lower than that of control rats. Binding of 3H-MeTRH at 2 nM concentration to membranes prepared from brain regions (striatum, hypothalamus, cortex, midbrain and pons plus medulla) of methimazole-treated and control rats did not differ. However, binding of 3H-MeTRH to pituitary membranes of methimazole-treated rats was significantly lower as compared to the pituitary of control rats. The results indicate that, in the rat, development of hypothyroidism is associated with down-regulation of pituitary TRH receptors but brain receptors remain unaffected.