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
An Increase in Kisspeptin-54 Release Occurs with the Pubertal Increase in Luteinizing Hormone-Releasing Hormone-1 Release in the Stalk-Median Eminence of Female Rhesus Monkeys in Vivo
TL;DR: The results indicate that a significant increase inkisspeptin-54 release occurred in association with the pubertal increase in LHRH-1 release and that a nocturnal increase in kisspeptin -54 release was already observed in prepubertal monkeys and continued through the Pubertal period.
Journal ArticleDOI
Kisspeptin Mediates the Photoperiodic Control of Reproduction in Hamsters
Florent G. Revel,Michel Saboureau,Mireille Masson-Pévet,Paul Pévet,Jens D. Mikkelsen,Valérie Simonneaux +5 more
TL;DR: It is proposed that photoperiod, via melatonin, modulates KiSS-1 signaling to drive the reproductive axis, consistent with a role of Ki SS1/GPR54 in the seasonal control of reproduction.
Journal ArticleDOI
Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling.
TL;DR: The Kiss1 gene codes for a family of peptides that act as endogenous ligands for the G protein-coupled receptor GPR54, suggesting that KiSS-1 neurons in this region may have a role in the preovulatory LH surge or sexual behavior.
Journal ArticleDOI
TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood
Elena Gianetti,Cintia Tusset,Sekoni D. Noel,Margaret G. Au,Andrew A. Dwyer,Virginia A. Hughes,Ana Paula Abreu,Jessica Carroll,Ericka B. Trarbach,Leticia Ferreira Gontijo Silveira,Elaine Maria Frade Costa,Berenice B. Mendonca,Margaret de Castro,Adriana Lofrano,Janet E. Hall,Erol Bolu,Metin Ozata,Richard Quinton,John K. Amory,Susan E. Stewart,Wiebke Arlt,Trevor Cole,William F. Crowley,Ursula B. Kaiser,Ana Claudia Latronico,Stephanie B. Seminara +25 more
TL;DR: Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time.
Journal ArticleDOI
Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2
Shunichiro Matsumoto,Chihiro Yamazaki,Koh-hei Masumoto,Mamoru Nagano,Masanori Naito,Takatoshi Soga,Hideki Hiyama,Mitsuyuki Matsumoto,Jun Takasaki,Masazumi Kamohara,Ayako Matsuo,Hiroyuki Ishii,Masato Kobori,Masao Katoh,Hitoshi Matsushime,Kiyoshi Furuichi,Yasufumi Shigeyoshi +16 more
TL;DR: It is demonstrated that physiological activation of PKR2 is essential for normal development of the OB and sexual maturation.
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