THYROTROPIN-RELEASING-HORMONE PRECURSOR - CHARACTERIZATION IN RAT-BRAIN
THYROTROPIN-RELEASING-HORMONE PRECURSOR - CHARACTERIZATION IN RAT-BRAIN
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DOI：
10.1126/science.3079917
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发表时间：
1986-01-10
期刊：
影响因子：
56.9
通讯作者：
GOODMAN, RH
中科院分区：
文献类型：
--
作者：
LECHAN, RM;WU, P;GOODMAN, RH
为了表征哺乳动物促甲状腺激素释放激素（TRH）的前体，用抗合成肽的抗血清筛选大鼠下丘脑gt 11文库，所述合成肽代表大鼠TRH激素原的一部分。免疫阳性互补DNA的核苷酸序列编码分子量为29，247的蛋白质。该蛋白含有5个拷贝的Gln-His-Pro-Gly序列，两侧是成对的碱性氨基酸，因此可以产生5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，这些肽可以被分泌。大鼠脑切片原位杂交表明，前proTRH互补DNA检测到的神经元集中在室旁核的小细胞分裂，免疫组化检测到的细胞相同的位置。这些发现表明，哺乳动物TRH产生的翻译后加工的一个更大的前体蛋白。TRH激素原产生多拷贝生物活性肽的能力可能是激素产生放大的重要机制。
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 5 copies of the sequence Gln-His-Pro-Gly flanked by paired basic amino acids and could therefore generate 5 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.