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
Citations
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Kisspeptin: A key link to seasonal breeding
Florent G. Revel,Laura Ansel,Paul Klosen,Michel Saboureau,Paul Pévet,Jens D. Mikkelsen,Valérie Simonneaux +6 more
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The neuroanatomy of the kisspeptin system in the mammalian brain.
TL;DR: The available data suggest that kisspeptins are synthesized in neurons in the anteroventral periventricular nucleus and the arcuate nucleus, and both populations are considered to be involved in control of gonadotropes.
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Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization
Channa N. Jayasena,Ali Abbara,Alexander N Comninos,Gurjinder Nijher,Georgios Christopoulos,Shakunthala Narayanaswamy,Chioma Izzi-Engbeaya,Mathini Sridharan,Alexina J. Mason,Jane Warwick,Deborah Ashby,Mohammad A. Ghatei,Stephen R. Bloom,Anna Carby,Geoffrey Trew,Waljit S. Dhillo +15 more
TL;DR: It is demonstrated that a single injection of kisspeptin-54 can induce egg maturation in women with subfertility undergoing in vitro fertilization therapy and subsequent fertilization of eggs matured and transfer of resulting embryos can lead to successful human pregnancy.
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Hypothalamic Expression of KISS1 and Gonadotropin Inhibitory Hormone Genes During the Menstrual Cycle of a Non-Human Primate
TL;DR: A role for kisspeptin in the stimulation of GnRH cells before the preovulatory GnRH/LH surge in non-human primates is suggested.
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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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