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Open AccessJournal ArticleDOI

A Role for Kisspeptins in the Regulation of Gonadotropin Secretion in the Mouse

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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.

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Book ChapterDOI

Kisspeptin and clinical disorders.

TL;DR: The human genetics of the kisspeptin signaling pathway in patients with diverse reproductive phenotypes will be explored and revealed, revealing the critical role played by thekisspeptin signaled pathway in pubertal initiation and reproductive function.
Journal ArticleDOI

Molecular cloning and characterization of KISS1 promoter and effect of KISS1 gene mutations on litter size in the goat.

TL;DR: The spectrum of genetic variation of the goat KISS1 gene is extended, which contributes to the knowledge of goat genetic resources for breeding programs, and cloned the promoter sequence of this gene found it to share high similarity with that of the bovine K ISS1 promoter.
Book ChapterDOI

Stress and the Reproductive System

TL;DR: There is increasing evidence that these stress neuropeptides affect the kisspeptin signaling system to compromise both GnRH pulse and surge generation, which are critical for reproductive function.
Journal ArticleDOI

Clinical Potential of Kisspeptin in Reproductive Health.

TL;DR: Kisspeptins are a family of hypothalamic neuropeptides that are essential for the regulation of reproductive physiology as mentioned in this paper, and their importance in reproductive health became apparent in 2003, when loss-of-function variants in the gene encoding the kisspeptin receptor were reported to result in isolated congenital hypogonadotropic hypogono-morphosis (CHH), and it has since been ascertained that hypothalamic kiss-peptin neurons regulate gonadotropin-releasing hormone (GnRH) secretion to stimulate the remainder of the reproductive end
Journal ArticleDOI

KISS1 is down-regulated by 17beta-estradiol in MDA-MB-231 cells through a nonclassical mechanism and loss of ribonucleic acid polymerase II binding at the proximal promoter.

TL;DR: E2 rapidly down-regulated endogenous KISS1 in a stable ERalpha-expressing MDA-MB-231 breast cancer cell line, which revealed that E2 down-regulation was determined by a short 93-bp sequence devoid of estrogen response element and Sp1 sites.
References
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Book

The Physiology of Reproduction

Ernst Knobil, +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

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

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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