Blockage of neonatal leptin signaling induces changes in the hypothalamus associated with delayed pubertal onset and modifications in neuropeptide expression during adulthood in male rats |
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| Institution: | 1. Department of Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense, Madrid, Spain;2. Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain;3. Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain;4. CIBER Fisiopatología de Obesidad y Nutrición, Instituto Carlos III, Madrid, Spain;1. Student Research Committee, Department of Modern Science and Technology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;2. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;3. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;4. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran;5. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran;6. Stem cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran;7. Biochemistry of Nutrition Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;8. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;9. Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran;1. Department of Paediatrics and Adolescent Medicine, University Hospital of Cologne, Cologne, Germany;2. Comparative Medicine, Center for Molecular Medicine, University of Cologne (CMMC), Cologne, Germany;1. Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada;2. Département des Sciences de l’Activité Physique, Université du Québec à Montréal, Montréal, Québec, Canada;3. Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada;4. Faculty of Health Science, Kiryu University, Midori, Gunma, Japan;5. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan;6. Faculty of Pharmacy, Université Laval, Québec, Québec, Canada;7. Faculty of Medicine, Université Laval, Québec, Québec, Canada;1. Department of Pharmacology, Shanxi Medical University, Taiyuan, China;2. Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China;3. Department of Pediatrics, Shanxi Medical University, Taiyuan, China;4. Department of Endocrinology, the First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, China |
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| Abstract: | The neonatal leptin surge, occurring from postnatal day (PND) 5 to 13 and peaking at PND9 in rodents, is important for the development of neuroendocrine circuits involved in metabolic control and reproductive function. We previously demonstrated that treatment with a leptin antagonist from PND 5 to 9, coincident with peak leptin levels in the neonatal surge, modified trophic factors and markers of cell turnover and neuronal maturation in the hypothalamus of peri-pubertal rats. The kisspeptin system and metabolic neuropeptide and hormone levels were also modified. Here our aim was to investigate if the timing of pubertal onset is altered by neonatal leptin antagonism and if the previously observed peripubertal modifications in hormones and neuropeptides persist into adulthood and affect male sexual behavior. To this end, male Wistar rats were treated with a pegylated super leptin antagonist (5 mg/kg, s.c.) from PND 5 to 9 and killed at PND102–103. The appearance of external signs of pubertal onset was delayed. Hypothalamic kiss1 mRNA levels were decreased in adult animals, but sexual behavior was not significantly modified. Although there was no effect on body weight or food intake, circulating leptin, insulin and triglyceride levels were increased, while hypothalamic leptin receptor, POMC and AgRP mRNA levels were decreased. In conclusion, alteration of the neonatal leptin surge can modify the timing of pubertal onset and have long-term effects on hypothalamic expression of reproductive and metabolic neuropeptides. |
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| Keywords: | Leptin antagonist Kisspeptin Puberty Sexual behavior |
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