Pu L P, Ma W, Barker J L, Loh Y P
Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, National Institutes of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892, USA.
Endocrinology. 1996 Apr;137(4):1233-41. doi: 10.1210/endo.137.4.8625894.
Pro-TRH is cleaved at paired basic residues to yield five copies of TRH and cryptic peptides. Recent studies have shown that the prohormone convertases, PC1 and PC2, can process pro-TRH correctly. To determine whether these two enzymes could play a role in pro-TRH processing in vivo, the regional and cellular colocalization of pro-TRH messenger RNA (mRNA) with the mRNAs encoding the prohormone convertases PC1 and PC2 was examined in rat brain, using in situ hybridization histochemistry. Differential regional distribution of pro-TRH mRNA with PC1 and/or PC2 mRNA was found in several brain regions. For example, in the olfactory regions, there was coexpression of pro-TRH mRNA in the glomerular layer with PC2 mRNA, but not PC1 mRNA, whereas in the tenia tecta, coexpression of pro-TRH and PC1 mRNAs was evident, but PC2 mRNA was absent. Pro-TRH mRNA in the paraventricular nucleus was coexpressed with both PC1 and PC2 mRNAs, whereas the basal lateral hypothalamus showed coexistence of pro-TRH mRNA with PC2 mRNA, but not PC1 mRNA. Interestingly, pro-TRH was expressed in the thalamic reticular nucleus, but neither PC1 nor PC2 was detectable in this region. Cellular colocalization studies using double in situ hybridization histochemistry showed the presence of PC2 mRNA in the pro-TRH neurons of the olfactory glomerular layer and basal lateral hypothalamus, and PC1 mRNA in the pro-TRH neurons in the paraventricular nucleus. These results suggest that PC1 and PC2 are enzyme candidates for the processing of pro-TRH in vivo. Moreover, the differential distribution of PC1 and PC2 mRNAs with pro-TRH mRNA may be responsible for the differential processing of this prohormone in the central nervous system. The absence of PC1 and PC2 mRNAs in certain TRH neurons raises the possibility that prohormone convertases other than PC1 and PC2 may be involved in the processing of brain pro-TRH.
促甲状腺激素释放激素原（Pro-TRH）在成对的碱性残基处被切割，产生五个拷贝的促甲状腺激素释放激素（TRH）和一些隐匿肽。最近的研究表明，激素原转化酶PC1和PC2能够正确加工Pro-TRH。为了确定这两种酶是否能在体内Pro-TRH的加工过程中发挥作用，利用原位杂交组织化学技术，在大鼠脑中检测了Pro-TRH信使核糖核酸（mRNA）与编码激素原转化酶PC1和PC2的mRNA的区域和细胞共定位情况。在几个脑区发现了Pro-TRH mRNA与PC1和/或PC2 mRNA的差异区域分布。例如，在嗅觉区域，在肾小球层中Pro-TRH mRNA与PC2 mRNA共表达，但不与PC1 mRNA共表达；而在终纹床核中，Pro-TRH和PC1 mRNA的共表达明显，但不存在PC2 mRNA。室旁核中的Pro-TRH mRNA与PC1和PC2 mRNA均共表达，而基底外侧下丘脑则显示Pro-TRH mRNA与PC2 mRNA共存，但不与PC1 mRNA共存。有趣的是，Pro-TRH在丘脑网状核中表达，但在该区域未检测到PC1和PC2。使用双重原位杂交组织化学的细胞共定位研究表明，在嗅觉肾小球层和基底外侧下丘脑的Pro-TRH神经元中存在PC2 mRNA，在室旁核的Pro-TRH神经元中存在PC1 mRNA。这些结果表明，PC1和PC2是体内加工Pro-TRH的候选酶。此外，PC1和PC2 mRNA与Pro-TRH mRNA的差异分布可能是该激素原在中枢神经系统中差异加工的原因。某些促甲状腺激素释放激素（TRH）神经元中不存在PC1和PC2 mRNA，这增加了除PC1和PC2之外的其他激素原转化酶可能参与脑内Pro-TRH加工的可能性。
