title: Colocalization of cocaine- and amphetamine-regulated transcript with kisspeptin and neurokinin B in the human infundibular region.
abstract: Kisspeptin (KP)- and neurokinin B (NKB)- synthesizing neurons of the hypothalamic arcuate nucleus play a pivotal role in the regulation of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Unlike in rodents and sheep, the homologous KP and NKB neurons in the human infundibular region rarely express dynorphin- but often exhibit Substance P (SP) immunoreactivity, indicating remarkable species differences in the neurochemical phenotype of these neurons. In search for additional neuropeptides in human KP and NKB neurons, we carried out immunofluorescent studies on hypothalamic sections obtained from five postmenopausal women. Colocalization experiments provided evidence for the presence of cocaine- and amphetamine-regulated transcript (CART) in 47.9 ± 6.6% of KP-immunoreactive (IR) and 30.0 ± 4.9% of NKB-IR perikarya and in 17.0 ± 2.3% of KP-IR and 6.2 ± 2.0% of NKB-IR axon varicosities. All three neuropeptides were present in 33.3 ± 4.9% of KP-IR and 28.2 ± 4.6% of NKB-IR somata, respectively, whereas triple-labeling showed lower incidences in KP-IR (14.3 ± 1.8%) and NKB-IR (5.9 ± 2.0%) axon varicosities. CART-IR KP and NKB neurons established contacts with other peptidergic cells, including GnRH-IR neurons and also sent projections to the infundibular stalk. KP and NKB fibers with CART often contained SP as well, while being distinct from CART fibers co-containing the orexigenic peptide agouti-related protein. Presence of CART in human, but not rodent, KP and NKB neurons represents a new example of species differences in the neuropeptide repertoire of mediobasal hypothalamic KP and NKB neurons. Target cells, receptor sites and physiological significance of CART in the efferent communication of KP and NKB neurons in primates require clarification.
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Skrapits
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine of the University of Debrecen, Debrecen, Hungary.
authors.forename: Beáta Á
authors.initials: BÁ
authors.lastname: Borsay
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine of the University of Debrecen, Debrecen, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Herczeg
authors.affiliation: INSERM U862, Neurocentre Magendie, Bordeaux, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ciofi
authors.affiliation: Department of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: Department of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.affiliation: Department of Investigative Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom.
authors.forename: Waljit S
authors.initials: WS
authors.lastname: Dhillo
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; Department of Neuroscience, Faculty of Information Technology, Pázmány Péter Catholic University, Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Liposits
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Erik
authors.initials: E
authors.lastname: Hrabovszky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D054369:Agouti-Related Protein / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D059648:Kisspeptins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015287:Neurokinin B / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D021381:Protein Transport; D013373:Substance P / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D054369:Agouti-Related Protein; C106628:KISS1 protein, human; D059648:Kisspeptins; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D013373:Substance P; D007987:Gonadotropin-Releasing Hormone; D015287:Neurokinin B
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