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ResearchIn-Press PreviewEndocrinologyReproductive biology
Open Access | 10.1172/JCI172908
1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
2Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Lille, France
3Departement of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
4Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America
5Reproductive Physiology Group; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
6Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America
7FIVAP, Centro de Fecundacion In Vitro Angela Palumbo, La Laguna, Spain
8Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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Published June 11, 2024 - More info
Reproduction is safeguarded by multiple, often cooperative regulatory networks. Kisspeptin signaling, via KISS1R, plays a fundamental role in reproductive control, primarily by regulation of hypothalamic GnRH neurons. We disclose herein a pathway for direct kisspeptin actions in astrocytes that contributes to central reproductive modulation. Protein-protein-interaction and ontology analyses of hypothalamic proteomic profiles after kisspeptin stimulation revealed that glial/astrocyte markers are regulated by kisspeptin in mice. This glial-kisspeptin pathway was validated by the demonstrated expression of Kiss1r in mouse astrocytes in vivo and astrocyte cultures from humans, rats and mice, where kisspeptin activated canonical intracellular signaling-pathways. Cellular co-expression of Kiss1r with the astrocyte markers, GFAP and S100-β, occurred in different brain regions, with higher percentage in Kiss1- and GnRH-enriched areas. Conditional ablation of Kiss1r in GFAP-positive cells, in the G-KiRKO mouse, altered gene expression of key factors in PGE2 synthesis in astrocytes, and perturbed astrocyte-GnRH neuronal appositions, as well as LH responses to kisspeptin and LH pulsatility, as surrogate marker of GnRH secretion. G-KiRKO mice also displayed changes in reproductive responses to metabolic stress induced by high-fat diet, affecting female pubertal onset, estrous cyclicity and LH-secretory profiles. Our data unveil a non-neuronal pathway for kisspeptin actions in astrocytes, which cooperates in fine-tuning the reproductive axis and its responses to metabolic stress.