| Gonadotropin releasing hormone (GnRH) is a decapeptide hormone, which is synthesized by the hypothalamic neuroendocrine cells and secreted through the hypothalamic-hypophyseal portal system into the pituitary anterior lobe in a pulsatile pattern, where it binds to the gonadotropin-releasing hormone receptor (GnRH-R) on the gonadotropin-secretory cells and stimulates the secretion of LH and FSH by the signaling pathway mediated by this receptor. So the blood concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary in a pulsatile way, and exert their effects on the gametogenesis in the gonad and the functions of target organs.GnRH was reported to originate in the vertebrates, and the datas suggested that there were two or more kinds of GnRH in the vertebrates, among them the Chicken GnRH II was the most broadly present type. And the fact that more than two types of GnRH exist in the vertebrates suggests that there may be*?* A*******different GnRH-R isoforms. Indeed, 4 GnRH molecules and 1 GnRH-R have been identified in mammals with 13 GnRH molecules and several GnRH-R identified in non-mammalian vertebrates, and the possibility that there be novel isoforms still remains. Among the 4 reported GnRH molecules, only the GnRH I (mammalian GnRH) and GnRH II (chicken GnRH II) were found to be expressed in human genome.The encoding sequences of GnRH precursors varied between different species. So far the sequences of GnRH precursors in human, mouse, rat, and xenopus have been identified. All of them had the same regulatory unit and 4 exons, suggesting that they shared the same ancestor gene. The human GnRH II and I located at the chromosome 8(8pll.2-p21) and 20(20pl3) locus respectively. The GnRH isoforms were found to be highly conservative in their length, NH2- terminus (residue 1,2,4) and COOH- terminus (residue 9,10).The residue 8 was the most common mutation site to be seen, followed by residue 5, 7,6, suggesting the possibility of posttranscriptional modification. The terminal residues proved critical for the bioactivity of GnRH. Accordingly, chemists developed many kinds of GnRH agonists and antagonists by modifying the structure of GnRH, which occupied the binding site on the target cells and hence regulated the subsequent signaling.GnRH-R is the main mediator of the GnRH functions. So far, the GnRH-Rs in mouse, rat, sheep, bull and human have been cloned and characterized, and a great homology was found between different species motioned above. GnRH-R belongs to the G protein coupled receptor family, and it is consisted of a polypeptide chain containing 7 transmembrane domains. The GnRH-R encodes 327/328 amino acids.Human GnRH-R gene contains three exons and two introns. Exon I-9-includes the 5'-terminal UTR and partial ORF (transmembrane domain I -III and part of domain IV). Exon II encodes the part of the domain IV and domain V, with exon III encodes the rest of the ORF and the 3'-terminal UTR. Intron A is 4.2 Kb in size and intron B less than 5.0 kb. The human GnRH -R gene has TATA box and CAAT box as well as other gene regulatory units, so more than one factors are involved in the regulation of the transcription and translation of GnRH-R. Moreover, the transcription and translation of GnRH-R are in rigid controlled by factors such as GnRH autocrine, Ganado-steroids. gonadotropin, activin and inhibin, etc.Recent studies showed that GnRH and its receptors exist in many tissue and organs outside of the hypothalamus-pituitary axis, for example, the gonad (ovary, testis, mammary gland, prostate), placent and adrenal cortex, and as in the mice, the stomach, intestine, pancreas and submandibular gland. The GnRH and its receptors exert diverse regulations on the functions of these organs. And also, the GnRH and GnRH-R were found in the cancers originated from both the gonad axis and outside the gonad axis such as ovarian cancer, lung cancer, pancreatic cancer and colon cancer.GnRH, when binding with its receptors of cancer, controls the growth of canc...
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