title: Disparate changes in kisspeptin and neurokinin B expression in the arcuate nucleus after sex steroid manipulation reveal differential regulation of the two KNDy peptides in rats.
abstract: Kisspeptin, neurokinin B (NKB) and dynorphin A are coexpressed in a population of neurons in the arcuate nucleus (ARC), termed KNDy neurons, which were recently recognized as important elements for the generation of GnRH pulses. However, the topographic distribution of these peptides and their regulated expression by sex steroids are still not well understood. In this study, detailed examination of NKB and kisspeptin immunoreactivity in the rat ARC was carried out, including comparison between sexes, with and without sex steroid replacement. Neurons expressing kisspeptin and NKB were more prominent in the caudal ARC of females, whereas neurons expressing NKB, but not kisspeptin, were the most abundant in the male. Sex steroid manipulation revealed differential regulation of kisspeptin and NKB; although kisspeptin immunoreactive (ir) cells increased in response to gonadectomy, NKB remained unchanged. Furthermore, the number of NKB-ir cells increased upon sex steroid replacement compared with gonadectomy, whereas kisspeptin did not, suggesting that sex steroids differently regulate these peptides. In addition, only in females did the density of kisspeptin- and NKB-ir fibers in the ARC increase upon sex steroid replacement in relation to sham and ovariectomy, respectively, suggesting sex-specific regulation of release. In conclusion, our observations reveal sex differences in the number of kisspeptin- and NKB-ir cells, which are more prominent in the caudal ARC. The divergent regulation of kisspeptin and NKB peptide contents in the ARC as a function of sex and steroid milieu enlarge our understanding on how these neuropeptides are posttranscriptionally regulated in KNDy neurons.
authors: Neurobiology Research Unit (A.O., J.D.M.), Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark; Department of Cell Biology, Physiology, and Immunology (F.R.-P., J.M.C., M.T.-S.), University of Córdoba, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (F.R.-P., M.T.-S.), Instituto de Salud Carlos III, and Instituto Maimónides de Investigación Biomédica de Córdoba/Hospital Universitario Reina Sofía (F.R.-P., M.T.-S.), 14004 Córdoba, Spain; and Division of Neuroscience (J.M.C.), Oregon National Primate Research Center, Beaverton, Oregon 97006.
authors: Agnete
authors: A
authors: Overgaard
authors: Francisco
authors: F
authors: Ruiz-Pino
authors: Juan M
authors: JM
authors: Castellano
authors: Manuel
authors: M
authors: Tena-Sempere
authors: Jens D
authors: JD
authors: Mikkelsen
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002369:Castration; D002452:Cell Count; D004399:Dynorphins / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology / Q000502:physiology*; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D015287:Neurokinin B / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
chemical_list: D012739:Gonadal Steroid Hormones; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D004399:Dynorphins; D015287:Neurokinin B