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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Journal ArticleDOI
Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats
Emily L. Thompson,Kevin G. Murphy,Michael Patterson,Gavin A. Bewick,Gordon Stamp,Annette E. Curtis,Jennifer H. Cooke,Preeti H. Jethwa,Jeannie Todd,Mohammad A. Ghatei,Stephen R. Bloom +10 more
TL;DR: In this paper, the effects of continuous peripheral kisspeptin administration in male rats by use of Alzet minipumps were investigated, and the results indicated that the peptide may provide a novel tool for the manipulation of the HPG axis and spermatogenesis.
Journal ArticleDOI
Positive, But Not Negative Feedback Actions of Estradiol in Adult Female Mice Require Estrogen Receptor α in Kisspeptin Neurons
Sharon L. Dubois,Maricedes Acosta-Martínez,M. R. DeJoseph,Andrew Wolfe,Sally Radovick,Ulrich Boehm,Janice H. Urban,Jon E. Levine +7 more
TL;DR: It is shown that ERα in kisspeptin neurons is required for the positive, but not negative feedback actions of E2 on GnRH/LH secretion in adult female mice, and it remains to be determined whether the failure of KERαKO mice to exhibit GnRH-LH surges reflects the role of ER α in the development of kisspept neurons, in the active signaling processes leading to the release of GnRH/.
Journal ArticleDOI
Significance of Neonatal Testicular Sex Steroids to Defeminize Anteroventral Periventricular Kisspeptin Neurons and the GnRH/LH Surge System in Male Rats
Tamami Homma,Mototsugu Sakakibara,Shunji Yamada,Mika Kinoshita,Kinuyo Iwata,Junko Tomikawa,Tetsuhiro Kanazawa,Hisanori Matsui,Yoshihiro Takatsu,Tetsuya Ohtaki,Hirokazu Matsumoto,Yoshihisa Uenoyama,Kei-ichiro Maeda,Hiroko Tsukamura +13 more
TL;DR: In this paper, the significance of neonatal testicular androgen to defeminize AVPV kisspeptin expression and the GnRH/LH surge-generating system was determined.
Journal ArticleDOI
KiSS-1 and GPR54 Genes are Co-Expressed in Rat Gonadotrophs and Differentially Regulated In Vivo by Oestradiol and Gonadotrophin-Releasing Hormone
TL;DR: It is demonstrated for the first time that, in the female rat pituitary, KiSS‐1 expression is up‐regulated by oestradiol, similarly to that seen in the anteroventral periventricular nucleus of the hypothalamus.
Book ChapterDOI
Neuroendocrine Control of the Ovarian Cycle of the Rat
TL;DR: This chapter takes a comprehensive approach in describing the understanding and, in some cases, the misunderstanding of the control of the ovarian cycle by the brain and its interaction with the anterior pituitary gland and ovaries.
References
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Book
The Physiology of Reproduction
Ernst Knobil,J. D. Neill +1 more
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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