title: Substance P immunoreactivity exhibits frequent colocalization with kisspeptin and neurokinin B in the human infundibular region.
abstract: Neurons synthesizing neurokinin B (NKB) and kisspeptin (KP) in the hypothalamic arcuate nucleus represent important upstream regulators of pulsatile gonadotropin-releasing hormone (GnRH) neurosecretion. In search of neuropeptides co-expressed in analogous neurons of the human infundibular nucleus (Inf), we have carried out immunohistochemical studies of the tachykinin peptide Substance P (SP) in autopsy samples from men (21-78 years) and postmenopausal (53-83 years) women. Significantly higher numbers of SP-immunoreactive (IR) neurons and darker labeling were observed in the Inf of postmenopausal women than in age-matched men. Triple-immunofluorescent studies localized SP immunoreactivity to considerable subsets of KP-IR and NKB-IR axons and perikarya in the infundibular region. In postmenopausal women, 25.1% of NKB-IR and 30.6% of KP-IR perikarya contained SP and 16.5% of all immunolabeled cell bodies were triple-labeled. Triple-, double- and single-labeled SP-IR axons innervated densely the portal capillaries of the infundibular stalk. In quadruple-labeled sections, these axons formed occasional contacts with GnRH-IR axons. Presence of SP in NKB and KP neurons increases the functional complexity of the putative pulse generator network. First, it is possible that SP modulates the effects of KP and NKB in axo-somatic and axo-dendritic afferents to GnRH neurons. Intrinsic SP may also affect the activity and/or neuropeptide release of NKB and KP neurons via autocrine/paracrine actions. In the infundibular stalk, SP may influence the KP and NKB secretory output via additional autocrine/paracrine mechanisms or regulate GnRH neurosecretion directly. Finally, possible co-release of SP with KP and NKB into the portal circulation could underlie further actions on adenohypophysial gonadotrophs.
authors: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. hrabovszky.erik@koki.hu
authors: Erik
authors: E
authors: Hrabovszky
authors: Beáta Á
authors: BÁ
authors: Borsay
authors: Kálmán
authors: K
authors: Rácz
authors: László
authors: L
authors: Herczeg
authors: Philippe
authors: P
authors: Ciofi
authors: Stephen R
authors: SR
authors: Bloom
authors: Mohammad A
authors: MA
authors: Ghatei
authors: Waljit S
authors: WS
authors: Dhillo
authors: Zsolt
authors: Z
authors: Liposits
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism*; D001369:Axons / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D066146:Cell Body / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D059648:Kisspeptins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015287:Neurokinin B / Q000032:analysis / Q000378:metabolism*; D010902:Pituitary Gland / Q000098:blood supply / Q000378:metabolism; D021381:Protein Transport; D013373:Substance P / Q000032:analysis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D059648:Kisspeptins; D013373:Substance P; D007987:Gonadotropin-Releasing Hormone; D015287:Neurokinin B
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