Differential regulation of basal and kindling-induced TRH mRNA expression by thyroid hormone in the hypothalamic and limbic structures.

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.