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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Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173
Lauren M. Stein,Chloe W. Tullock,Stacy K. Mathews,David Garcia-Galiano,Carol F. Elias,Willis K. Samson,Gina L. C. Yosten +6 more
TL;DR: These studies are the first to demonstrate a functional relationship between PNX and Gpr173 in reproductive physiology and identify a potential therapeutic target for ovulatory dysfunction.
Journal ArticleDOI
Metastin and its G protein-coupled receptor, GPR54: critical pathway modulating GnRH secretion.
TL;DR: The recent identification of loss-of-function mutations in GPR54, a receptor for kisspeptin-1, has highlighted a new pathway for the timing of puberty and reproductive control.
Journal ArticleDOI
Leptin is not the Critical Signal for Kisspeptin or Luteinising Hormone Restoration During Exit from Negative Energy Balance
TL;DR: Results suggest that, although leptin may be a permissive signal for reproductive function, hypoleptinaemia is unlikely to be the critical signal responsible for ARC Kiss1 and LH inhibition during negative energy balance.
Journal ArticleDOI
Kisspeptin neurons from mice to men: similarities and differences.
TL;DR: Recent data on the similarities and differences across several mammalian species in the role of kisspeptin in reproductive neuroendocrinology are reviewed to have significance for understanding normal neuroendocrine control of reproduction as well as for use ofkisspeptin agonists/antagonists as a therapeutic tool.
Journal ArticleDOI
The generation of an array of clonal, immortalized cell models from the rat hypothalamus: analysis of melatonin effects on kisspeptin and gonadotropin-inhibitory hormone neurons
Sarah Gingerich,X. Wang,P.K.P. Lee,Sandeep S. Dhillon,Jennifer A. Chalmers,Margaret M. Koletar,Denise D. Belsham +6 more
TL;DR: These cell lines will serve as novel tools for the analysis of the cellular and molecular mechanisms involved in hypothalamic control of a number of physiological processes described in the rat animal model.
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The Physiology of Reproduction
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TL;DR: The gametes, fertilization and early embryogenesis the reproductive systems - the female, the male the pituitary and the hypothalmus, and the reproductive processes and their control.
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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