Cunningham Matthew J, Scarlett Jarrad M, Steiner Robert A
Graduate Program in Neurobiology & Behavior, University of Washington, Seattle, Washington 98195-7290, USA.
Endocrinology. 2002 Mar;143(3):755-63. doi: 10.1210/endo.143.3.8661.
Galanin-like peptide (GALP) is a newly discovered hypothalamic neuropeptide, which is regulated by leptin and implicated in the regulation of GnRH secretion in the rodent. We searched the human genome database and determined that the human GALP gene comprises six exons, as has been shown for human galanin. We used rapid amplification of cDNA ends to clone a full-length cDNA (802 bp) of the macaque homologue of GALP and found it to be highly conserved between human and macaque at both the nucleotide (93%) and peptide (94%) levels. Mature GALP is predicted to be 60 amino acids in the macaque as in other species, and the region of GALP (9-21) that shows homology to the N-terminal 13 amino acids of galanin is perfectly conserved. We mapped the distribution of GALP mRNA in the hypothalamus and pituitary of the macaque by in situ hybridization and observed that, as in rodent species, the expression of GALP mRNA is confined to the arcuate nucleus, median eminence, and neurohypophysis. Using double-label in situ hybridization, we found that nearly all (98%) GALP mRNA-expressing cells in the arcuate nucleus also express mRNA for the long form of the leptin receptor. These findings suggest that a leptin-GALP signaling pathway exists in a primate species.
甘丙肽样肽(GALP)是一种新发现的下丘脑神经肽,受瘦素调节,参与啮齿动物促性腺激素释放激素(GnRH)分泌的调节。我们检索了人类基因组数据库,确定人类GALP基因包含六个外显子,这与人类甘丙肽的情况一致。我们使用cDNA末端快速扩增技术克隆了GALP猕猴同源物的全长cDNA(802 bp),发现其在核苷酸水平(93%)和肽水平(94%)上在人类和猕猴之间高度保守。与其他物种一样,预测猕猴成熟GALP为60个氨基酸,并且GALP中与甘丙肽N端13个氨基酸具有同源性的区域(9-21)完全保守。我们通过原位杂交绘制了GALP mRNA在猕猴下丘脑和垂体中的分布,观察到与啮齿动物一样,GALP mRNA的表达局限于弓状核、正中隆起和神经垂体。使用双标记原位杂交,我们发现弓状核中几乎所有(98%)表达GALP mRNA的细胞也表达长型瘦素受体的mRNA。这些发现表明灵长类动物中存在瘦素-GALP信号通路。