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
Reads0
Chats0
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
More filters
Journal ArticleDOI
The GPR54 gene as a regulator of puberty
Stephanie B. Seminara,Sophie Messager,Emmanouella E. Chatzidaki,Rosemary R. Thresher,James S. Acierno,Jenna K. Shagoury,Yousef Bo-Abbas,Wendy Kuohung,Kristine M. Schwinof,Alan G. Hendrick,Dirk Zahn,John Dixon,Ursula B. Kaiser,Susan A. Slaugenhaupt,James F. Gusella,Stephen O'Rahilly,Mark Carlton,William F. Crowley,Samuel Aparicio,William H. Colledge +19 more
TL;DR: Puberty is initiated when gonadotropin-releasing hormone begins to be secreted by the hypothalamus, and complementary genetic approaches in humans and mice identified genetic factors that determine the onset of puberty.
Journal ArticleDOI
EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals
Andrea C. Gore,Vesna A. Chappell,Suzanne E. Fenton,Jodi A. Flaws,Angel Nadal,Gail S. Prins,Jorma Toppari,R. T. Zoeller +7 more
TL;DR: A much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, can be much better translated to human health.
Journal ArticleDOI
Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54
Sophie Messager,Emmanouella E. Chatzidaki,Dan Ma,Alan G. Hendrick,Dirk Zahn,John Dixon,Rosemary R. Thresher,Isabelle Malinge,Didier Lomet,Mark B. L. Carlton,William H. Colledge,Alain Caraty,Samuel Aparicio +12 more
TL;DR: GPR54 is defined as a major control point in the reproductive axis and kisspeptin is suggested to be a neurohormonal effector, demonstrating that a key action ofkisspeptin on the hypothalamo-pituitary-gonadal axis occurs directly at the level of GnRH release.
Journal ArticleDOI
Advances in male contraception.
TL;DR: Great strides have been made in understanding male reproductive physiology; the combined efforts of scientists, clinicians, industry and governmental funding agencies could make an effective, reversible, male contraceptive an option for family planning over the next decade.
Journal ArticleDOI
A Role for Kisspeptins in the Regulation of Gonadotropin Secretion in the Mouse
Michelle L. Gottsch,Matthew Cunningham,Jeremy Troy Smith,Simina M. Popa,Blake V. Acohido,William F. Crowley,Stephanie B. Seminara,Donald K. Clifton,Robert A. Steiner +8 more
TL;DR: Kisspeptins are products of the KiSS-1 gene, which bind to a G protein-coupled receptor known as GPR54, and it is concluded that kisspeptin-GPR54 signaling may be part of the hypothalamus circuitry that governs the hypothalamic secretion of GnRH.
References
More filters
Journal ArticleDOI
Characterization of a cDNA encoding a novel avian hypothalamic neuropeptide exerting an inhibitory effect on gonadotropin release.
Honoo Satake,Miki Hisada,Tsuyoshi Kawada,Hiroyuki Minakata,Kazuyoshi Ukena,Kazuyoshi Tsutsui +5 more
TL;DR: GnIH is a hypothalamic factor responsible for the negative regulation of gonadotropin secretion and the presence of a novel RFamide peptide family containing a C-terminal -LPXRF-NH(2) sequence has been revealed.
Journal ArticleDOI
Molecular Basis of Combined Pituitary Hormone Deficiencies
Laurie E. Cohen,Sally Radovick +1 more
TL;DR: Pituitary gland commitment from oral ectoderm occurs in response to inductive signals from the neuroepithelium of the ventral diencephalon, and highly differentiated cell types arise sequentially due to overlapping, but distinct, spatial and temporal patterns of signaling molecules and transcription factors.
Journal ArticleDOI
Transcriptional Expression of Genes Involved in Cell Invasion and Migration by Normal and Tumoral Trophoblast Cells
Jean-Louis Janneau,Juan G Maldonado-Estrada,Juan G Maldonado-Estrada,Gérard Tachdjian,Isabelle Miran,Nelly Motté,Patrick Saulnier,Jean-Christophe Sabourin,Jean-François Côté,Bénédicte Simon,René Frydman,Gérard Chaouat,Dominique Bellet,Dominique Bellet +13 more
TL;DR: In this article, the authors measured the transcriptional expression profiles of trophoblast cells in early and term placentas and found that expression levels of BRMS1 and KiSS-1R were higher in term than in early placenta.
Journal ArticleDOI
The Eph family in the patterning of neural development.
TL;DR: Characteristics of the Eph family are extended promiscuity in the interaction between receptors and ligands, the necessity of membrane attachment of the ligands to exert their function, the lack of induction of mitogenic responses, and the bi-directional signalling of receptors and binds.
Journal ArticleDOI
Expression of basigin, a member of the immunoglobulin superfamily, in the mouse central nervous system.
Qi-Wen Fan,Shigeki Yuasa,Naohiko Kuno,Takao Senda,Miya Kobayashi,Takashi Muramatsu,Kenji Kadomatsu +6 more
TL;DR: It is shown by means of in situ hybridization that Bsg mRNA was expressed in neuroblasts in 13.5 day old mouse embryos, and Northern blot analysis confirmed the strong expression of Bsg in the central nervous system.
Related Papers (5)
The GPR54 gene as a regulator of puberty
Stephanie B. Seminara,Sophie Messager,Emmanouella E. Chatzidaki,Rosemary R. Thresher,James S. Acierno,Jenna K. Shagoury,Yousef Bo-Abbas,Wendy Kuohung,Kristine M. Schwinof,Alan G. Hendrick,Dirk Zahn,John Dixon,Ursula B. Kaiser,Susan A. Slaugenhaupt,James F. Gusella,Stephen O'Rahilly,Mark Carlton,William F. Crowley,Samuel Aparicio,William H. Colledge +19 more
The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.
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