Bhargava H N, Ramarao P, Gulati A, Matwyshyn G A, Prasad R
Department of Pharmacodynamics, Radioimmunoassay Laboratory, University of Illinois, Chicago.
Pharmacology. 1989;38(4):243-52. doi: 10.1159/000138543.
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.
测定了甲状腺功能减退对大鼠多个脑区及垂体中促甲状腺激素释放激素（TRH）受体的影响。用³H-（³-MeHis²）TRH（³H-MeTRH）标记TRH受体。通过在雄性Sprague-Dawley大鼠饮用水中给予甲巯咪唑（0.05% w/v）32天来诱导甲状腺功能减退。作为对照的大鼠给予不含甲巯咪唑的水。与对照大鼠相比，结肠温度、收缩压、心率以及血清三碘甲状腺原氨酸（总T3）、甲状腺素和T3摄取（T3U）浓度显著降低，证明甲状腺功能减退状态的发展。甲巯咪唑处理的大鼠体重增加速率显著低于对照大鼠。在2 nM浓度下，³H-MeTRH与甲巯咪唑处理大鼠及对照大鼠脑区（纹状体、下丘脑、皮质、中脑和脑桥加延髓）制备的膜的结合没有差异。然而，与对照大鼠的垂体相比，³H-MeTRH与甲巯咪唑处理大鼠垂体膜的结合显著降低。结果表明，在大鼠中，甲状腺功能减退的发展与垂体TRH受体的下调有关，但脑受体未受影响。
