The binding of 3H-(3-MeHis2) thyrotropin releasing hormone to brain and pituitary membranes of hyperthyroid rats

Abstract

The effect of chronic treatment of male Sprague-Dawley rats with thyroxine (1 mg/kg, s.c., every other day) for 18 days on the brain and pituitary receptors for thyrotropin releasing hormone (TRH) labeled with 3H-(3-MeHis2)TRH (3H-MeTRH) was determined. Rats serving as controls received the injection of the vehicle for thyroxine. Chronic administration of thyroxine resulted in the development of hyperthyroidism as evidenced by slower rate of gain of body weight, increased colonic temperature, increased systolic blood pressure and heart rate in comparison to vehicle-injected rats. The development of hyperthyroidism by thyroxine treatment was also evidenced by increases in the serum concentration of triiodothyronine (total T3) and thyroxine (T4) in comparison to vehicle-injected rats. The binding of 3H-MeTRH to membranes prepared from different brain regions (striatum, hypothalamus, pons + medulla, cortex and midbrain) and pituitary membranes of thyroxine-treated and untreated rats was determined at 2 nM concentration. The binding of 3H-MeTRH to membranes prepared from any brain region of thyroxine-treated and untreated rats did not differ. The binding of 3H-MeTRH to pituitary membranes of thyroxine-treated rats was much greater than that of untreated rats. It is concluded that chronic administration of thyroxine to rats leads to the development of hyperthyroid state as evidenced by both physiological and biochemical indices, and that hyperthyroid state does not alter the TRH receptors in the hypothalamus or any other brain region but the pituitary TRH receptors are up-regulated.