Lechan R M, Wu P, Jackson I M, Wolf H, Cooperman S, Mandel G, Goodman R H
Science. 1986 Jan 10;231(4734):159-61. doi: 10.1126/science.3079917.
To characterize the precursor of mammalian thyrotropin-releasing hormone (TRH), a rat hypothalamic lambda gt11 library was screened with an antiserum directed against a synthetic peptide representing a portion of the rat TRH prohormone. The nucleotide sequence of the immunopositive complementary DNA encoded a protein with a molecular weight of 29,247. This protein contained five copies of the sequence Gln-His-Pro-Gly flanked by paired basic amino acids and could therefore generate five TRH molecules. In addition, potential cleavage sites in the TRH precursor could produce other non-TRH peptides, which may be secreted. In situ hybridization to rat brain sections demonstrated that the pre-proTRH complementary DNA detected neurons concentrated in the parvocellular division of the paraventricular nucleus, the same location as cells detected by immunohistochemistry. These findings indicate that mammalian TRH arises by posttranslational processing of a larger precursor protein. The ability of the TRH prohormone to generate multiple copies of the bioactive peptide may be an important mechanism in the amplification of hormone production.
为了鉴定哺乳动物促甲状腺激素释放激素（TRH）的前体，用针对代表大鼠TRH原激素一部分的合成肽的抗血清筛选大鼠下丘脑λgt11文库。免疫阳性互补DNA的核苷酸序列编码一种分子量为29247的蛋白质。该蛋白质含有五个Gln-His-Pro-Gly序列拷贝，两侧为成对的碱性氨基酸，因此可以产生五个TRH分子。此外，TRH前体中的潜在切割位点可以产生其他非TRH肽，这些肽可能会被分泌。对大鼠脑切片进行原位杂交表明，前促TRH互补DNA检测到的神经元集中在室旁核的小细胞部，与免疫组织化学检测到的细胞位置相同。这些发现表明，哺乳动物的TRH是由一种更大的前体蛋白经翻译后加工产生的。TRH原激素产生多个生物活性肽拷贝的能力可能是激素产生放大的重要机制。
