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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Evidence That Dynorphin Acts Upon KNDy and GnRH Neurons During GnRH Pulse Termination in the Ewe
Peyton W. Weems,Lique M. Coolen,Stanley M. Hileman,Steven L. Hardy,Richard B McCosh,Robert L. Goodman,Michael N. Lehman +6 more
TL;DR: Results indicate that Dyn is released onto KNDy cells at the time of pulse onset, and continues to be released during the duration of the pulse, compared to MBH GnRH neurons only at pulse termination, and thus actions of Dyn upon K NDy and GnRH cell bodies may be critical for pulse termination.
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Functional analysis of kisspeptin peptides in adult immature chub mackerel (Scomber japonicus) using an intracerebroventricular administration method
Hirofumi Ohga,Sethu Selvaraj,Hayato Adachi,Yui Imanaga,Mitsuo Nyuji,Akihiko Yamaguchi,Michiya Matsuyama +6 more
TL;DR: Results suggested that synthetic Kiss2-12 could induce transcriptional changes in gnrh1 and gths during the immature stage of adult chub mackerel (2+ years old), and kisspeptins encoded by the Kiss1 gene could act as upstream endogenous regulators of GnRH neurons in mammals.
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Expression of KiSS-1 in rat oviduct: possible involvement in prevention of ectopic implantation?
María Gaytán,Juan M. Castellano,Juan Carlos Roa,José E. Sánchez-Criado,Manuel Tena-Sempere,Francisco Gaytan +5 more
TL;DR: Knowing the regional- and cycle-specific pattern of expression of KiSS-1 in rat oviduct should open up the possibility of a physiological role of kisspeptins in the prevention of ectopic (tubal) implantation.
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Genetic counseling for isolated GnRH deficiency
TL;DR: This chapter offers a guide to incorporating this rapidly evolving state of knowledge of the pedigree and phenotypes into the process of selecting and prioritizing genetic testing.
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The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function.
L A Owens,Ali Abbara,A Lerner,S O'floinn,Georgios Christopoulos,Shirin Khanjani,Rumana Islam,Kate Hardy,Aylin C. Hanyaloglu,Stuart Lavery,Waljit S. Dhillo,Stephen Franks +11 more
TL;DR: The use of kisspeptin-54 as an oocyte maturation trigger augmented expression of genes involved in ovarian steroidogenesis in human GL cells when compared to traditional maturation triggers, but did not alter markers of OHSS.
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