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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TRANSCRIPTIONAL REGULATION OF THE HUMAN KiSS1 GENE
Johanna K. Mueller,Anja Dietzel,Alejandro Lomniczi,Alberto Loche,Katrin Tefs,Wieland Kiess,Thomas Danne,Sergio R. Ojeda,Sabine Heger,Sabine Heger +9 more
TL;DR: It is shown that a set of proteins postulated to be upstream components of a hypothalamic network involved in controlling female puberty regulates KiSS1 transcriptional activity, suggesting that expression of the Ki SS1 gene is regulated by trans-activators and repressors involved in the system-wide control of mammalian puberty.
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Comparative Evolutionary Histories of Kisspeptins and Kisspeptin Receptors in Vertebrates Reveal Both Parallel and Divergent Features
Jérémy Pasquier,Anne-Gaëlle Lafont,Hervé Tostivint,Hubert Vaudry,Karine Rousseau,Sylvie Dufour +5 more
TL;DR: Comparisons of recently published genomes from species of phylogenetic interest revealed un-matching numbers of Kiss and Kissr genes in some species, as well as a large variability of Kiss/Kissr couples according to species, which support independent features of the Kiss andkissr evolutionary histories across vertebrates.
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The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1).
TL;DR: In vitro and in vivo models used to study the role that insulin and IGF-1 play in controlling the hypothalamus and pituitary and their role in regulating puberty and nutritional control of reproduction are summarized.
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Anatomy of the kisspeptin systems in teleosts.
Satoshi Ogawa,Ishwar S. Parhar +1 more
TL;DR: The existence of two kisspeptin systems suggests their independent functions in the brain of teleosts and their potential roles in reproductive and non-reproductive functions are discussed.
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Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition.
TL;DR: It is documented that AMPK and SIRT1 operate as major molecular effectors for the metabolic control of Kiss1 neurons and, thereby, puberty onset, and might become druggable targets for better management of pubertal disorders.
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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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Tetsuya Ohtaki,Yasushi Shintani,Susumu Honda,Hirokazu Matsumoto,Akira Hori,Kimiko Kanehashi,Yasuko Terao,Satoshi Kumano,Yoshihiro Takatsu,Yasushi Masuda,Yoshihiro Ishibashi,Takuya Watanabe,Mari Asada,Takao Yamada,Masato Suenaga,Chieko Kitada,Satoshi Usuki,Tsutomu Kurokawa,Haruo Onda,Osamu Nishimura,Masahiko Fujino +20 more
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