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
A single injection of kisspeptin-54 temporarily increases luteinizing hormone pulsatility in healthy women.
Channa N. Jayasena,Alexander N Comninos,Johannes D. Veldhuis,Shivani Misra,Shivani Misra,Ali Abbara,Chioma Izzi-Engbeaya,M. Donaldson,M. A. Ghatei,Stephen R. Bloom,Waljit S. Dhillo +10 more
TL;DR: A single subcutaneous bolus injection of kisspeptin‐54 increases circulating luteinizing hormone (LH) levels in women, but its acute effects on LH pulsatility are not known.
Journal ArticleDOI
Etiology and treatment of hypogonadism in adolescents.
TL;DR: The causes of hypogonadism are heterogeneous and may involve any level of the reproductive system, and treatment options for the induction of puberty in affected adolescents are outlined.
Journal ArticleDOI
Prenatal Exposure to Low Levels of Androgen Accelerates Female Puberty Onset and Reproductive Senescence in Mice
TL;DR: Pregnant, but not prepubertal, exposure to low levels of androgens disrupts normal reproductive function throughout life from puberty to reproductive senescence, and the absence of kisspeptin receptor in Kiss1r-null mice did not change the acceleration of puberty by the PNA and PPA paradigms.
Book ChapterDOI
Neuroendocrine Control of the Menstrual Cycle
TL;DR: The pattern of regular ovulatory cycles required for normal reproduction in women is achieved through precise functional and temporal integration of stimulatory and inhibitory signals from the hypothalamus, the pituitary, and the ovary.
Journal ArticleDOI
Central Mechanism Controlling Pubertal Onset in Mammals: A Triggering Role of Kisspeptin.
TL;DR: It is envisage that negative feedback action of estrogen plays a key role in the inhibition of Kiss1 expression in KNDy neurons in rodents and sheep, whereas estrogen-independent inhibition of kisspeptin secretion by γ-amino butyric acid or neuropeptide Y are suggested to be responsible for the pre-pubertal suppression of GnRH/gonadotropin secretion in primates.
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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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