Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
Nicolas de Roux,Emmanuelle Génin,Jean Claude Carel,Fumihiko Matsuda,Chaussain Jl,Edwin Milgrom +5 more
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TLDR
The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR 54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.Abstract:
Hypogonadotropic hypogonadism is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. In the absence of pituitary or hypothalamic anatomical lesions and of anosmia (Kallmann syndrome), hypogonadotropic hypogonadism is referred to as isolated hypogonadotropic hypogonadism (IHH). A limited number of IHH cases are due to loss-of-function mutations of the gonadotropin-releasing hormone receptor. To identify additional gene defects leading to IHH, a large consanguineous family with five affected siblings and with a normal gonadotropin-releasing hormone receptor coding sequence was studied. Homozygosity whole-genome mapping allowed the localization of a new locus within the short arm of chromosome 19 (19p13). Sequencing of several genes localized within this region showed that all affected siblings of the family carried a homozygous deletion of 155 nucleotides in the GPR54 gene. This deletion encompassed the splicing acceptor site of intron 4-exon 5 junction and part of exon 5. The deletion was absent or present on only one allele in unaffected family members. GPR54 has been initially identified as an orphan G protein-coupled receptor with 40% homology to galanin receptors. Recently, a 54-aa peptide derived from the KiSS1 protein was identified as a ligand of GPR54. The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.read more
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Alterations in hypothalamic KiSS-1 system in experimental diabetes: early changes and functional consequences.
Juan M. Castellano,Víctor M. Navarro,Juan Carlos Roa,Rafael Pineda,Miguel A. Sánchez-Garrido,David Garcia-Galiano,E. Vigo,Carlos Dieguez,Enrique Aguilar,Leonor Pinilla,Manuel Tena-Sempere +10 more
TL;DR: The present findings further define the temporal course and mechanistic relevance of altered hypothalamic KiSS-1 system in the hypogonadotropic state of uncontrolled diabetes and provide the basis for the potential therapeutic intervention of the Ki SS1 system as adjuvant in the management of disturbed gonadotropin secretion of type 1 diabetes in the female.
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Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands
Shinya Oishi,Ryosuke Misu,Kenji Tomita,Shohei Setsuda,Ryo Masuda,Hiroaki Ohno,Yousuke Naniwa,Nahoko Ieda,Naoko Inoue,Satoshi Ohkura,Yoshihisa Uenoyama,Hiroko Tsukamura,Kei-ichiro Maeda,Akira Hirasawa,Gozoh Tsujimoto,Nobutaka Fujii +15 more
TL;DR: The possible localization of secondary kisspeptin targets was demonstrated by variation in the levels of GnRH release from the median eminence and the type of GPR54 agonists used, which indicates the unidirectional cross-reactivity between both ligands.
Journal ArticleDOI
Molecular coevolution of kisspeptins and their receptors from fish to mammals
TL;DR: Together, kisspeptin and GPR54 provide an excellent model for understanding molecular coevolution of the peptide ligand and GPCR pairs.
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The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.
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