title: 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.
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 (5mg/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.
authors.affiliation: Department of Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense, Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Mela
authors.affiliation: Department of Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Jimenez
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain; CIBER Fisiopatología de Obesidad y Nutrición, Instituto Carlos III, Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Freire-Regatillo
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain; CIBER Fisiopatología de Obesidad y Nutrición, Instituto Carlos III, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Barrios
authors.affiliation: Department of Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense, Madrid, Spain.
authors.forename: Eva-María
authors.initials: EM
authors.lastname: Marco
authors.affiliation: Department of Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense, Madrid, Spain.
authors.forename: Ana-Belén
authors.initials: AB
authors.lastname: Lopez-Rodriguez
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain; CIBER Fisiopatología de Obesidad y Nutrición, Instituto Carlos III, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.affiliation: Department of Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense, Madrid, Spain.
authors.forename: María-Paz
authors.initials: MP
authors.lastname: Viveros
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain; CIBER Fisiopatología de Obesidad y Nutrición, Instituto Carlos III, Madrid, Spain. Electronic address: julieann.chowen@salud.madrid.org.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000378:metabolism; D012726:Sexual Behavior, Animal; D012741:Sexual Maturation; D015398:Signal Transduction; D015430:Weight Gain; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D059648:Kisspeptins; D020738:Leptin; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D054411:Receptors, Leptin; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin
keywords: Kisspeptin; Leptin antagonist; Puberty; Sexual behavior