Kim S Y, Post R M, Rosen J B
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Md., USA.
Neuroendocrinology. 1996 Mar;63(3):297-304. doi: 10.1159/000126969.
It has previously been demonstrated that thyrotropin-releasing hormone (TRH) mRNA expression is dramatically increased in limbic structures including dentate gyrus granular layer, and pyriform, entorhinal and perirhinal cortices following amygdala kindling. Since thyroid hormone regulates TRH mRNA in the paraventricular nucleus of the hypothalamus (PVN), we investigated whether basal or kindling-induced TRH mRNA expression in limbic regions is also regulated by thyroid hormone. Hypo- and hyperthyroidism was induced by treating rats with 0.05% 6-n-propyl-2-thiouracil (PTU) (equivalent to approximately 30 mg/kg/day) or 0.9 microM 3,5,3'-triiodo-L-thyronine (T3) (equivalent to approximately 50 micrograms/kg/day), respectively, in their drinking water for 10 days before kindling and throughout the kindling procedure. Rats were sacrificed 4 h after their first stage 5 seizure. None of the thyroid hormone manipulations altered kindling development, or behavioral and electrographic after-discharge seizure durations. Pituitary TSH beta mRNA levels were significantly increased by PTU and suppressed by T3, but unaffected by kindling. In addition, in situ hybridization showed that PTU administration increased and T3 administration decreased TRH mRNA levels in the PVN, consistent with thyroid hormone's negative feedback effects. At the same time, kindling had no effect on TRH mRNA in the PVN. In contrast, kindling dramatically increased TRH mRNA in the dentate gyrus granular layer, and pyriform, entorhinal and perirhinal cortices, but thyroid hormone manipulations did not affect either basal or kindling-induced TRH mRNA expression in limbic structures. These findings demonstrate that TRH mRNA expression is differentially regulated in the hypothalamic PVN and limbic structures.
先前已经证明，在杏仁核点燃后，促甲状腺激素释放激素（TRH）mRNA表达在包括齿状回颗粒层、梨状皮质、内嗅皮质和嗅周皮质在内的边缘结构中显著增加。由于甲状腺激素调节下丘脑室旁核（PVN）中的TRH mRNA，我们研究了边缘区域中基础或点燃诱导的TRH mRNA表达是否也受甲状腺激素调节。在点燃前10天及整个点燃过程中，分别用0.05%的6-正丙基-2-硫氧嘧啶（PTU）（相当于约30 mg/kg/天）或0.9 μM的3,5,3'-三碘-L-甲状腺原氨酸（T3）（相当于约50 μg/kg/天）处理大鼠饮用水10天，以诱导甲状腺功能减退和亢进。大鼠在首次出现5级癫痫发作后4小时处死。甲状腺激素处理均未改变点燃发展、行为和脑电图后放电癫痫持续时间。垂体TSHβmRNA水平在PTU处理后显著升高，在T3处理后受到抑制，但不受点燃影响。此外，原位杂交显示，给予PTU会增加PVN中的TRH mRNA水平，给予T3会降低TRH mRNA水平，这与甲状腺激素的负反馈作用一致。同时，点燃对PVN中的TRH mRNA没有影响。相比之下，点燃显著增加了齿状回颗粒层、梨状皮质、内嗅皮质和嗅周皮质中的TRH mRNA，但甲状腺激素处理对边缘结构中基础或点燃诱导的TRH mRNA表达均无影响。这些发现表明，TRH mRNA表达在下丘脑PVN和边缘结构中受到不同的调节。
