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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Journal ArticleDOI
Effects of Pinealectomy and Short Day Lengths on Reproduction and Neuronal RFRP-3, Kisspeptin, and GnRH in Female Turkish Hamsters.
David J. Piekarski,Stephan G. Jarjisian,Luz Perez,Huzaifa Ahmad,Namita Dhawan,Irving Zucker,Lance J. Kriegsfeld,Lance J. Kriegsfeld +7 more
TL;DR: Reproductive quiescence, whether induced by short-day lengths or pinealectomy, was generally accompanied by comparable changes in RFRP-3 and kisspeptin, suggesting that long-duration melatonin signaling and withdrawal of melatonin by Pinealectomy may act through the same neural substrates to induce gonadal quiescent.
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Kisspeptin Expression in the Human Infundibular Nucleus in Relation to Sex, Gender Identity, and Sexual Orientation
Mélanie Taziaux,Annemieke S. Staphorsius,Mohammad A. Ghatei,Stephen R. Bloom,Dick F. Swaab,Julie Bakker +5 more
TL;DR: Findings suggest that infundibular kisspeptin neurons are sensitive to circulating sex steroid hormones throughout life and that the sex reversal observed in MTF transsexuals might reflect, at least partially, an atypical brain sexual differentiation.
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The role of the hypothalamus and pituitary epigenomes in central activation of the reproductive axis at puberty.
Dor Shalev,Philippa Melamed +1 more
TL;DR: Epigenetic mechanisms which have been demonstrated in the KNDy neurons that increase the output of pulsatile GnRH, and those involved in activation of the GnRH gene and its receptor are addressed, and how GnRH utilizes epigenetic mechanisms to stimulate transcription of the pituitary gonadotropin genes in the context of the chromatin landscape is described.
Journal ArticleDOI
Altered expression of the kisspeptin/KISS1R and neurokinin B/NK3R systems in mural granulosa and cumulus cells of patients with polycystic ovarian syndrome.
Víctor Blasco,Francisco M. Pinto,Ainhoa Fernández-Atucha,Nicolás Prados,Manuel Tena-Sempere,Manuel Fernández-Sánchez,Luz Candenas +6 more
TL;DR: The NKB/NK3R and KISS1/KISS1R systems are dysregulated in MGCs and CCs of PCOS women and the lower expression of these systems in GCs could contribute to the abnormal follicle development and defective ovulation that characterize the pathogenesis ofPCOS.
Journal ArticleDOI
Clinical assessment and molecular analysis of GnRHR and KAL1 genes in males with idiopathic hypogonadotrophic hypogonadism
Beatriz R. Versiani,Ericka B. Trarbach,Marcel Koenigkam-Santos,Antonio Carlos dos Santos,Lucila Leico Kagohara Elias,Ayrton Custódio Moreira,Ana Claudia Latronico,Margaret de Castro +7 more
TL;DR: The clinical findings and molecular analysis of GnRHR and KAL1 genes in 26 Brazilian males with IHH with and without hyposmia/anosmia are characterized.
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