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人促黄体生成激素释放激素前体的cDNA特性分析

Characterization of cDNA for precursor of human luteinizing hormone releasing hormone.

作者信息

Seeburg P H, Adelman J P

出版信息

Nature. 1984;311(5987):666-8. doi: 10.1038/311666a0.

DOI:10.1038/311666a0
PMID:6090951
Abstract

Human reproduction is controlled by the hypothalamic-pituitary-gonadal axis laid down early in fetal development. Luteinizing hormone releasing hormone (LHRH), also termed gonadotropin releasing hormone (GnRH), is a decapeptide and is a key molecule in this control circuit. It is produced by hypothalamic neurones, secreted in a pulsatile manner into the capillary plexus of the median eminence and effects the release of luteinizing hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary. The peptide may have further functions, including behavioural ones, as LHRH or LHRH-like immunoreactivity has been found in gonadal tissue, placenta and the central nervous system, and exogenously administered LHRH is shown to affect behaviour. To investigate the biosynthesis of LHRH, we have now isolated cloned genomic and cDNA sequences encoding the precursor form of LHRH, the existence of which had been suggested from chromatographic studies of hypothalamic and placental extracts. These DNA sequences code for a protein of 92 amino acids in which the LHRH decapeptide is preceded by a signal peptide of 23 amino acids and followed by a Gly-Lys-Arg sequence, as expected for enzymatic cleavage of the decapeptide from its precursor and amidation of the carboxy-terminal of LHRH.

摘要

人类生殖受胎儿发育早期就已形成的下丘脑 - 垂体 - 性腺轴控制。促黄体生成素释放激素(LHRH),也称为促性腺激素释放激素(GnRH),是一种十肽,是这一控制回路中的关键分子。它由下丘脑神经元产生,以脉冲方式分泌到正中隆起的毛细血管丛中,并影响垂体前叶促性腺细胞释放促黄体生成素和促卵泡激素。该肽可能还有其他功能,包括行为方面的功能,因为在性腺组织、胎盘和中枢神经系统中发现了LHRH或LHRH样免疫反应性,并且外源性给予LHRH会影响行为。为了研究LHRH的生物合成,我们现已分离出编码LHRH前体形式的克隆基因组和cDNA序列,下丘脑和胎盘提取物的色谱研究已提示其存在。这些DNA序列编码一种92个氨基酸的蛋白质,其中LHRH十肽之前是一个23个氨基酸的信号肽,之后是一个甘氨酸 - 赖氨酸 - 精氨酸序列,这与从其前体酶切十肽并使LHRH羧基末端酰胺化的预期一致。

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