Sánchez E, Uribe R M, Corkidi G, Zoeller R T, Cisneros M, Zacarias M, Morales-Chapa C, Charli J L, Joseph-Bravo P
Departmento Genética y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca/Mor., México.
Neuroendocrinology. 2001 Dec;74(6):407-22. doi: 10.1159/000054707.
Thyrotropin-releasing hormone (TRH) is released from the median eminence upon neural stimulation such as cold or suckling exposure. Concomitant with the cold- or suckling-induced release of TRH is a rapid and transient increase in the expression of proTRH mRNA in the paraventricular nucleus (PVN) of the hypothalamus. We employed two strategies to determine whether TRH neurons responding to cold exposure are different from those responding to suckling. First, we attempted to identify a marker of cellular activation in TRH neurons of the PVN. Cold induced c-fos expression in about 25% of TRH neurons of the PVN, but no induction was observed by suckling. Moreover, we explored the expression of a variety of immediate early genes including NGFI-A, fra-1 and c-jun, or CREB phosphorylation but found none to be induced by suckling. The number of cells expressing high levels of proTRH mRNA was counted and compared to total expressing cells. An increased number of cells expressing high levels of proTRH mRNA was observed when both stimuli were applied to the same animal, suggesting that different cells respond separately to each stimulus. We therefore analyzed the distribution of responsive TRH neurons as defined by the cellular level of proTRH mRNA. The proTRH mRNA signal was analyzed within three rostrocaudal zones of the PVN and within six mediolateral columns. Results showed that in response to cold, all areas of the PVN of the lactating rat present increased proTRH mRNA levels, including the anterior zone where few hypophysiotropic TRHergic cells are believed to reside. The distribution of the proTRH mRNA expressing cells in response to cold was quite comparable in female and in male rats. In contrast, the response after suckling was confined to the middle and caudal zones. Our results provide evidence of a functional specialization of TRH cells in the PVN.
促甲状腺激素释放激素(TRH)在诸如寒冷或哺乳等神经刺激下从中位隆起释放。与寒冷或哺乳诱导的TRH释放同时发生的是,下丘脑室旁核(PVN)中proTRH mRNA的表达迅速且短暂增加。我们采用了两种策略来确定对寒冷暴露有反应的TRH神经元是否与对哺乳有反应的TRH神经元不同。首先,我们试图确定PVN中TRH神经元细胞激活的标志物。寒冷诱导PVN中约25%的TRH神经元表达c-fos,但哺乳未观察到诱导作用。此外,我们研究了包括NGFI-A、fra-1和c-jun在内的多种即刻早期基因的表达,或CREB磷酸化情况,但发现哺乳均未诱导这些基因表达。对表达高水平proTRH mRNA的细胞数量进行计数,并与总表达细胞进行比较。当两种刺激应用于同一只动物时,观察到表达高水平proTRH mRNA的细胞数量增加,这表明不同的细胞对每种刺激分别做出反应。因此,我们分析了由proTRH mRNA细胞水平定义的反应性TRH神经元的分布。在PVN的三个 rostrocaudal 区域和六个内外侧柱内分析了proTRH mRNA信号。结果表明,对寒冷的反应中,泌乳大鼠PVN的所有区域proTRH mRNA水平均升高,包括据信很少有促垂体TRH能细胞存在的前部区域。雌性和雄性大鼠中,对寒冷有反应的表达proTRH mRNA的细胞分布相当。相反,哺乳后的反应局限于中部和尾部区域。我们的结果提供了PVN中TRH细胞功能特化的证据。