Hökfelt T, Tsuruo Y, Ulfhake B, Cullheim S, Arvidsson U, Foster G A, Schultzberg M, Schalling M, Arborelius L, Freedman J
Department of Histology, Karolinska Institute, Stockholm, Sweden.
Ann N Y Acad Sci. 1989;553:76-105. doi: 10.1111/j.1749-6632.1989.tb46633.x.
During the last years, several important advancements have been made that are of importance for our understanding of the distribution and localization of neurons and cells producing TRH-LI. As detailed in other chapters in this volume, the precursor for TRH has been characterized that has allowed production of antibodies raised against specific sequences of this precursor. This, in turn, has provided new tools for the immunohistochemical elucidation of TRH systems in the CNS. The TRH precursor has also been cloned, leading to possibilities for studying the localization of TRH mRNA with in situ hybridization. Finally, as shown in this paper, improvement of the fixation technique has made it possible to visualize extensive TRH-immunoreactive cell body and fiber systems with antiserum raised against the TRH tripeptide. The results from the latter studies and those with antisera directed to the TRH precursor and in situ hybridization are in good agreement, with some minor exceptions. It should be pointed out that some of the systems described here, for example TRH positive-cell bodies in cortical areas and the hippocampal formation, contain only a very weak immunoreactivity. As always with immunohistochemical techniques, the possibility of crossreactivity with TRH-like peptides or TRH-like sequences within larger proteins must be considered. The present results confirm the presence of TRH-LI in the insulin-producing beta cells of the pancreas, which with the improved technique can be demonstrated also in early adulthood in rats and guinea pigs. Moreover, it could be established that TRH-LI is present in neurons in the gastrointestinal tract as well as in a population of endocrine cells in the antrum of the stomach of the guinea pig. These cells seem at least partly to be identical to the well-known gastrin-producing cells. TRH-LI has been observed to occur in neurons already containing a classical transmitter and/or other peptides. Of particular importance here seems to be a descending bulbospinal system that in addition to TRH co-contains 5-HT, substance P-LI, galanin-LI, human growth hormone immunoreactive material, and proctolin-like material. The significance of this coexistence is not well understood, but interesting interactions have been observed. Attempts to manipulate the TRH phenotype in these medullary neurons by transplantation to other sites in the brain has so far shown that the expression of this peptide seems fairly stable.(ABSTRACT TRUNCATED AT 400 WORDS)
在过去几年中，取得了几项重要进展，这对于我们理解产生促甲状腺激素释放激素样免疫活性物质（TRH-LI）的神经元和细胞的分布及定位至关重要。正如本卷其他章节所详述的，TRH的前体已被鉴定，这使得能够制备针对该前体特定序列的抗体。反过来，这为中枢神经系统中TRH系统的免疫组织化学阐明提供了新工具。TRH前体也已被克隆，从而有可能通过原位杂交研究TRH mRNA的定位。最后，如本文所示，固定技术的改进使得利用针对TRH三肽产生的抗血清可视化广泛的TRH免疫反应性细胞体和纤维系统成为可能。后一项研究的结果以及针对TRH前体的抗血清和原位杂交的结果基本一致，只有一些小的例外。应该指出的是，这里描述的一些系统，例如皮质区域和海马结构中的TRH阳性细胞体，仅含有非常弱的免疫反应性。与免疫组织化学技术一样，必须考虑与TRH样肽或较大蛋白质内TRH样序列交叉反应的可能性。目前的结果证实了胰腺中产生胰岛素的β细胞中存在TRH-LI，采用改进技术在大鼠和豚鼠成年早期也能证实这一点。此外，可以确定TRH-LI存在于胃肠道的神经元以及豚鼠胃窦中的一群内分泌细胞中。这些细胞似乎至少部分与著名的产生胃泌素的细胞相同。已观察到TRH-LI存在于已经含有经典递质和/或其他肽的神经元中。这里特别重要的似乎是一个下行延髓脊髓系统，除了TRH外，还共含有5-羟色胺、P物质样免疫活性物质、甘丙肽样免疫活性物质、人生长激素免疫反应性物质和类普罗托林物质。这种共存的意义尚未完全理解，但已观察到有趣的相互作用。迄今为止，通过将这些延髓神经元移植到脑内其他部位来操纵TRH表型的尝试表明，这种肽的表达似乎相当稳定。（摘要截选至400字）
