Characterization of Kiss1 neurons using transgenic mouse models

Cravo, R.M.; Margatho, L.O.; Osborne-Lawrence, S.; Donato, J.; Atkin, S.; Bookout, A.L.; Rovinsky, S.; Frazão, R.; Lee, C.E.; Gautron, L.; Zigman, J.M.; Elias, C.F.

doi:10.1016/j.neuroscience.2010.11.022

Cited by 353Hypothalamic control of reproductive hormonesRegulation of Appetite and ObesityNeuropeptides and Animal Physiology

Characterization of Kiss1 neurons using transgenic mouse models

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Cravo, R.M., Margatho, L.O., Osborne-Lawrence, S., Donato, J., Atkin, S., Bookout, A.L., Rovinsky, S., Frazão, R. +4 more·2011·Neuroscience

DOI 10.1016/j.neuroscience.2010.11.022PMC PMC3026459

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Abstract

Humans and mice with loss-of-function mutations of the genes encoding kisspeptins (Kiss1) or kisspeptin receptor (Kiss1r) are infertile due to hypogonadotropic hypogonadism. Within the hypothalamus, Kiss1 mRNA is expressed in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (Arc). In order to better study the different populations of kisspeptin cells we generated Kiss1-Cre transgenic mice. We obtained one line with Cre activity specifically within Kiss1 neurons (line J2-4), as assessed by generating mice with Cre-dependent expression of green fluorescent protein or β-galactosidase. Also, we demonstrated Kiss1 expression in the cerebral cortex and confirmed previous data showing Kiss1 mRNA in the medial nucleus of amygdala and anterodorsal preoptic nucleus. Kiss1 neurons were more concentrated towards the caudal levels of the Arc and higher leptin-responsivity was observed in the most caudal population of Arc Kiss1 neurons. No evidence for direct action of leptin in AVPV Kiss1 neurons was observed. Melanocortin fibers innervated subsets of Kiss1 neurons of the preoptic area and Arc, and both populations expressed melanocortin receptors type 4 (MC4R). Specifically in the preoptic area, 18-28% of Kiss1 neurons expressed MC4R. In the Arc, 90% of Kiss1 neurons were glutamatergic, 50% of which also were GABAergic. In the AVPV, 20% of Kiss1 neurons were glutamatergic whereas 75% were GABAergic. The differences observed between the Kiss1 neurons in the preoptic area and the Arc likely represent neuronal evidence for their differential roles in metabolism and reproduction.

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GnRH and kisspeptin neurons express various glutamate and GABA receptors and respond to these neurotransmitters.
“Even though estradiol is considered the main regulator of gonadotropin release, GnRH and kisspeptin neurons express various glutamate and GABA receptors and respond to these neurotransmitters [100,101].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [101]
Discussion §4.4 says GnRH neurons have GABA and glutamate receptors and that manipulating them changes GnRH and LH secretion. Results §3.5 shows that subsets of Kiss1 neurons express markers of GABA or glutamate production, but does not show that kisspeptin neurons express receptors for, or respond to, those neurotransmitters. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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Critical fatness hypothesis
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Untitled work
Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4

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Regulation of Arcuate Neurons Coexpressing Kisspeptin, Neurokinin B, and Dynorphin by Modulators of Neurokinin 3 and κ-Opioid Receptors in Adult Male Mice
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Molecular Properties of Kiss1 Neurons in the Arcuate Nucleus of the Mouse
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Effects of Leptin and Melanocortin Signaling Interactions on Pubertal Development and Reproduction
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Dominant Neuropeptide Cotransmission in Kisspeptin-GABA Regulation of GnRH Neuron Firing Driving Ovulation
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Kisspeptins and RFRP-3 Act in Concert to Synchronize Rodent Reproduction with Seasons
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Conditional kisspeptin neuron-specific Kiss1 knockout with newly generated Kiss1-floxed and Kiss1-Cre mice replicates a hypogonadal phenotype of global Kiss1 knockout mice
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Authors: Cravo, R. M., Margatho, L. O., Osborne-Lawrence, S., Donato, J., Atkin, S., Bookout, A. L., Rovinsky, S., Frazão, R., Lee, C. E., Gautron, L., Zigman, J. M., & Elias, C. F.
Affiliations: The University of Texas Southwestern Medical Center (US)
Universidade de São Paulo (BR)
Corresponding author: Elias, C.F.
ORCID: Osborne-Lawrence, S.
Donato, J.
Atkin, S.
Frazão, R.
Zigman, J.M.
Elias, C.F.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2011-01
Volume: 173
Pages: 37-56
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2010.11.022
PMC: PMC3026459
OpenAlex: W1992174470
Cited by: 353
References: 98
Citations by year: 2026: 7 · 2025: 16 · 2024: 21 · 2023: 21 · 2022: 24 · 2021: 35 · 2020: 18 · 2019: 34 · 2018: 18 · 2017: 22 · 2016: 19 · 2015: 22 · 2014: 29 · 2013: 29 · 2012: 18
FWCI: 25.15
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (R01DA024680)
National Institute of General Medical Sciences (T32GM007062, GM007062)
National Institute of Diabetes and Digestive and Kidney Diseases (K08DK068069)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD061539)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: kisspeptin neurons, KISS1, KISS1R, arcuate nucleus, anteroventral periventricular nucleus, preoptic area, medial amygdala, melanocortin-4 receptor, glutamatergic neurons, GABAergic neurons, hypothalamus, hypogonadotropic hypogonadism, reproduction, metabolism
MeSH terms: Animals, Brain, Cell Separation, Disease Models, Animal, Female, Flow Cytometry, Immunohistochemistry, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Proteins, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Mice, Kisspeptins

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Characterization of Kiss1 neurons using transgenic mouse models

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