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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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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Book ChapterDOI
Hormones and Reproductive Cycles in Primates
TL;DR: This chapter summarizes the current perspectives and understanding of reproductive function in human and nonhuman primates, including the hypothalamic-pituitary-gonadal (HPG) axis function across the lifespan; pregnancy and lactation; sexual behavior and its hormonal underpinnings; and seasonal, social, and energetic influences on reproduction.
Journal ArticleDOI
The kisspeptin receptor: A key G-protein-coupled receptor in the control of the reproductive axis.
TL;DR: A succinct summary of some of the most salient facets of Kiss1R, as essential GPCR for the proper maturation and function of the reproductive axis is provided.
Journal ArticleDOI
Sexual differentiation of kisspeptin neurons responsible for sex difference in gonadotropin release in rats.
TL;DR: It is plausible that perinatal testicular androgen causes defeminization of the AVPV kisspeptin system, resulting in the loss of the surge system in male rats.
Journal ArticleDOI
Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells.
Tomohiro Terasaka,Fumio Otsuka,Naoko Tsukamoto,Eri Nakamura,Kenichi Inagaki,Kishio Toma,Kanako Ogura-Ochi,Christine A. Glidewell-Kenney,Mark A. Lawson,Hirofumi Makino +9 more
TL;DR: The results indicate that the axis of kisspeptin-induced GnRH production is bi-directionally controlled, being augmented by an interaction between ERα/β and GPR54 signaling and suppressed by BMP-4 action in GT1-7 neuron cells.
Journal ArticleDOI
Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers.
Channa N. Jayasena,Alexander N Comninos,G. M.K. Nijher,Ali Abbara,A. De Silva,Johannes D. Veldhuis,Risheka Ratnasabapathy,Chioma Izzi-Engbeaya,Adrian Lim,Dhara A. Patel,M. A. Ghatei,Stephen R. Bloom,Waljit S. Dhillo +12 more
TL;DR: It is suggested that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women, and further work is needed to determine whetherkisspeptin could be used to treat certain anovulatory 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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TL;DR: Stimulation of oxytocin secretion after kisspeptin administration to rats confirmed this hypothesis that human GPR54 was highly expressed in placenta, pituitary, pancreas, and spinal cord, suggesting a role in the regulation of endocrine function.
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Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.
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
TL;DR: It is shown that KiSS-1 encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which is isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and named ‘metastin’.
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