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
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TLDR
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.Abstract:
Kisspeptins are products of the KiSS-1 gene, which bind to a G protein-coupled receptor known as GPR54. Mutations or targeted disruptions in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice, suggesting that kisspeptin signaling may be important for the regulation of gonadotropin secretion. To examine the effects of kisspeptin-54 (metastin) and kisspeptin-10 (the biologically active C-terminal decapeptide) on gonadotropin secretion in the mouse, we administered the kisspeptins directly into the lateral cerebral ventricle of the brain and demonstrated that both peptides stimulate LH secretion. Further characterization of kisspeptin-54 demonstrated that it stimulated both LH and FSH secretion, at doses as low as 1 fmol; moreover, this effect was shown to be blocked by pretreatment with acyline, a potent GnRH antagonist. To learn more about the functional anatomy of kisspeptins, we mapped the distribution of KiSS-1 mRNA in the hypothalamus. We observed that KiSS-1 mRNA is expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. We conclude that kisspeptin-GPR54 signaling may be part of the hypothalamic circuitry that governs the hypothalamic secretion of GnRH.read more
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A high-throughput small-molecule ligand screen targeted to agonists and antagonists of the G-protein-coupled receptor GPR54.
Wendy Kuohung,Maria Burnett,Deepa Mukhtyar,Eli R. Schuman,Jake Ni,William F. Crowley,Marcie A. Glicksman,Ursula B. Kaiser +7 more
TL;DR: A cell-based functional assay for high-throughput screening (HTS) and secondary screening will be characterized to identify agents with the potential to be developed as novel orally active agents to treat hormone-dependent disorders such as abnormal puberty, infertility, endometriosis, and sex steroid-dependent tumors.
Journal ArticleDOI
Kisspeptin/G protein-coupled receptor-54 system as an essential gatekeeper of pubertal development
TL;DR: Whether the kisspeptin/GPR54 system is the trigger for puberty onset and/or it operates as integrator and effector of up-stream regulatory factors warrants further investigation.
Journal ArticleDOI
Demonstration of a Functional Kisspeptin/Kisspeptin Receptor System in Amphioxus With Implications for Origin of Neuroendocrine Regulation
TL;DR: The presence of a functional kisspeptin/kisspeptin receptor (Kiss-Kissr) system, which is involved in the regulation of reproduction in amphioxus, is demonstrated and insights are provided into the functional roles and evolutionary history of the Kiss-KISSr system.
Journal ArticleDOI
Age-dependent elevations in plasma kisspeptin are observed in boys and girls when compared with adults
Channa N. Jayasena,Gurjinder M. K. Nijher,Shakunthala Narayanaswamy,Akila De Silva,Ali Abbara,Mohammad A. Ghatei,Stephen R. Bloom,Nicola Bridges,Waljit S. Dhillo +8 more
TL;DR: It is reported that circulating kisspeptin is elevated in both girls and boys aged 9–12 when compared with adults, and both boys and girls may have distinct, age-dependent concentrations of circulatingkisspeptin.
Journal ArticleDOI
Neurokinin B Causes Acute GnRH Secretion and Repression of GnRH Transcription in GT1–7 GnRH Neurons
Christine A. Glidewell-Kenney,Paul P. Shao,Anita K. Iyer,Anna M. H. Grove,Jason D. Meadows,Pamela L. Mellon +5 more
TL;DR: Data indicate that NKB could directly regulate secretion from NK3R-expressing GnRH neurons, and whether the response is inhibitory or stimulatory toward GnRH secretion could depend on the history or length of exposure to NKB because of a repressive effect on GnRH transcription.
References
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The Physiology of Reproduction
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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
Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system.
TL;DR: Comparing the distribution of the classical and novel forms of ER mRNA‐expressing neurons in the central nervous system (CNS) of the rat with in situ hybridization histochemistry provides evidence that the region‐specific expression of ER‐α, ER‐β, or both may be important in determining the physiological responses of neuronal populations to estrogen action.
Journal ArticleDOI
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
TL;DR: 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.
Journal ArticleDOI
Distribution of androgen and estrogen receptor mRNA‐containing cells in the rat brain: An in situ hybridization study
TL;DR: AR and ER may modulate nonolfactory sensory information as well since labeled cells were found in regions involved in the central relay of somatosensory information, including the mesencephalic nucleus of the trigeminal nerve, the ventral thalamic nuclear group, and the dorsal horn of the spinal cord.
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